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1
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Sultan H, Arshad N, Lateef M. Novel Crown Ether-Functionalized Fusidic Acid Butyl Ester: Synthesis, Biological Evaluation, In Silico ADMET, and Molecular Docking Studies. Molecules 2025; 30:2033. [PMID: 40363837 PMCID: PMC12073497 DOI: 10.3390/molecules30092033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2025] [Revised: 04/18/2025] [Accepted: 04/30/2025] [Indexed: 05/15/2025] Open
Abstract
Crown ethers have gained importance in the field of medicine because of their resemblance to natural ionophores like valinomycin. With the goal of developing new pharmacologically important crown ethers, a novel series of crown ethers linked with Fusidic acid butyl ester 10a-d were synthesized and characterized by means of their 1H NMR, 13C NMR DEPT-135, FT-IR, and mass spectrometry. In vitro antioxidant and α-glucosidase inhibition activities of all crown ethers along with the precursor Fusidic acid butyl ester were examined and compared to the standard butylated hydroxyanisole and acarbose, respectively. Compounds (FABE-16-crown-4) 10b and (FABE-19-crown-5) 10c showed high antioxidant potential with the IC50 = 22.5 ± 0.2 μM and 32.1 ± 0.3 μM, respectively, when compared to the standard BHA (IC50 = 44.2 ± 0.34 μM). To understand the binding mode of the compounds, molecular docking investigations were performed using human antioxidant protein, peroxiredoxin 5. Molecular docking studies revealed higher docking scores (-6.5 and -6.7 kcal/mol) for the highly active compounds 10c and 10b, respectively, than standard BHA (-5.3 kcal/mol). Synthesized crown ethers exhibited moderate α-glucosidase inhibition with (IC50 = 23.5 ± 0.2 to 76.5 ± 0.1 μM) when compared to acarbose as standard (IC50 = 5.2 ± 0.8 μM). The in silico ADMET predictions indicated that the prepared compounds obeyed (bRO5) and Veber's rule for the acceptance as orally administered drugs and indicated that all the prepared crown ethers exhibited calculated values of drug likeness parameters in acceptable ranges that showed good potential of these molecules for further drug development investigations.
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Affiliation(s)
- Hira Sultan
- Department of Chemistry, NED University of Engineering and Technology, Karachi 75270, Pakistan;
| | - Nuzhat Arshad
- Department of Chemistry, NED University of Engineering and Technology, Karachi 75270, Pakistan;
| | - Mehreen Lateef
- Multidisciplinary Lab, Bahria University of Karachi, Karachi 75270, Pakistan;
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2
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Santos G, Delgado E, Silva B, Braz BS, Gonçalves L. Topical Ocular Drug Delivery: The Impact of Permeation Enhancers. Pharmaceutics 2025; 17:447. [PMID: 40284442 PMCID: PMC12030643 DOI: 10.3390/pharmaceutics17040447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 03/20/2025] [Accepted: 03/26/2025] [Indexed: 04/29/2025] Open
Abstract
Topical ophthalmic drug delivery targeting the posterior segment of the eye has become a key area of interest due to its non-invasive nature, safety, ease of application, patient compliance, and cost-effectiveness. However, achievement of effective drug bioavailability in the posterior ocular segment is a significant challenge due to unique ocular barriers, including precorneal factors and anatomical barriers, like the cornea, the conjunctiva, and the sclera. Successful ocular drug delivery systems require increased precorneal residence time and improved corneal penetration to enhance intraocular bioavailability. A promising strategy to overcome these barriers is incorporating drug penetration enhancers (DPEs) into formulations. These compounds facilitate drug delivery by improving permeability across otherwise impermeable or poorly permeable membranes. At the ocular level, they act through three primary mechanisms: breaking tear film stability by interfering with the mucous layer; disrupting membrane components such as phospholipids and proteins; and loosening epithelial cellular junctions. DPEs offer significant potential to improve bioavailability and therapeutic outcomes, particularly for drugs targeting the posterior segment of the eye. This review is focused on analyzing the current literature regarding the use of penetration enhancers in topical ocular drug delivery, highlighting their mechanisms of action and potential to revolutionize ophthalmic treatments.
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Affiliation(s)
- Gonçalo Santos
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal;
- CIISA—Centro de Investigação Interdisciplinar em Saúde Animal, Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal; (E.D.); (B.S.); (B.S.B.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Esmeralda Delgado
- CIISA—Centro de Investigação Interdisciplinar em Saúde Animal, Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal; (E.D.); (B.S.); (B.S.B.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Beatriz Silva
- CIISA—Centro de Investigação Interdisciplinar em Saúde Animal, Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal; (E.D.); (B.S.); (B.S.B.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Berta São Braz
- CIISA—Centro de Investigação Interdisciplinar em Saúde Animal, Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal; (E.D.); (B.S.); (B.S.B.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Lídia Gonçalves
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal;
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3
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Paolino M, Saletti M, Venditti J, Zacchei A, Donati A, Bonechi C, Giuliani G, Lamponi S, Cappelli A. Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita-Baylis-Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity. Pharmaceuticals (Basel) 2025; 18:473. [PMID: 40283910 PMCID: PMC12030125 DOI: 10.3390/ph18040473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/20/2025] [Accepted: 03/21/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Crown ethers have received increasing interest owing to their ability to form stable complexes with cations. This molecular feature has been successfully exploited in the development of biologically relevant ionophores. Methods: In order to obtain innovative crown ethers derivatives, a Morita-Baylis-Hillman adduct (MBHA) acetate (4) bearing a phenylacetylene moiety was dimerized via the click-chemistry CuAAC reaction with oligo(ethylene glycol) diazide derivatives to build-up a small series of dimeric MBHA derivatives (5a-d). These dimeric MBHA derivatives were reacted with n-butylamine to afford tunable macrocyclic crown ether-paracyclophane hybrid architectures (6a-d). Results: Compounds (E,Z)-6a, (E,E)-6a, 6b-d showed, in human breast cancer MDA-MB-231 and human melanoma A375 cells, IC50 values comparable with those of reference anticancer agent Doxorubicin. Conclusions: This exploration approach provides original new macrocyclic architectures potentially useful as anticancer agents.
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Affiliation(s)
- Marco Paolino
- Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via Aldo Moro 2, 53100 Siena, Italy (A.C.)
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Wang Q, Huang W, Sun Q, Le M, Cai L, Jia YG. Facially amphiphilic skeleton-derived antibacterial crown ether/silver ion complexes. SOFT MATTER 2025; 21:2152-2159. [PMID: 39989433 DOI: 10.1039/d4sm01192a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
Silver and its derivatives have been widely explored for their antibacterial properties in the treatment of bacterial infections. However, the biological toxicity of silver limits its further development and application. In this study, we designed a facially amphiphilic skeleton incorporating crown ether moieties based on the dendrimer D-CA6-CE. The high-density crown ether units within this structure enable the chelation of silver ions, forming facially amphiphilic skeleton-derived D-CA6-CE/Ag+ complexes. These results indicate that D-CA6-CE/Ag+ can self-assemble into nano-micelles in aqueous solution. D-CA6-CE/Ag+ exhibited high antibacterial activity against Escherichia coli and Staphylococcus aureus, significantly reducing the minimum inhibitory concentrations (MICs) of Ag+ to 6.13 ± 0.19 and 7.33 ± 0.13 μg mL-1, respectively. This antibacterial efficacy surpassed that of silver sulfadiazine, primarily attributed to the enhanced ability to disturb and destroy bacterial membranes by introducing the amphiphilic structure of the cholic acid units. In addition, D-CA6-CE/Ag+ also exhibited lower hemolysis (approximately four times lower) and reduced cytotoxicity compared to silver sulfadiazine. This was likely due to the micellar structure formed by D-CA6-CE/Ag+, which further decreases the direct contact between Ag+ and cells. In summary, the D-CA6-CE/Ag+ complex, with its facially amphiphilic skeletons, exhibited superior antibacterial performance and lower biological toxicity than silver sulfadiazine does. These properties highlight its potential as a promising candidate for the treatment of bacterial infections.
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Affiliation(s)
- Qingsheng Wang
- Orthopedics Department, General Hospital of Pingmei Shenma Group, Pingdingshan 467000, China
| | - Wen Huang
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China
| | - Qian Sun
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China
| | - Mengqi Le
- School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China
| | - Lili Cai
- School of Life Science, Zhuhai College of Science and Technology, Zhuhai 519040, China.
| | - Yong-Guang Jia
- Center for Advanced Materials Research, Beijing Normal University, Zhuhai 519087, China.
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5
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Arenaza‐Corona A, Sánchez‐Portillo P, González‐Sebastián L, Sánchez‐Mora A, Monroy‐Torres B, Ramírez‐Apan T, Puentes‐Díaz N, Alí‐Torres J, Barba V, Reyes‐Marquez V, Morales‐Morales D. Water-Soluble Curcumin Derivatives Including Aza-Crown Ether Macrocycles as Enhancers of Their Cytotoxic Activity. Chem Biodivers 2025; 22:e202402083. [PMID: 39429102 PMCID: PMC11908749 DOI: 10.1002/cbdv.202402083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/12/2024] [Accepted: 10/16/2024] [Indexed: 10/22/2024]
Abstract
The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.
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Affiliation(s)
- Antonino Arenaza‐Corona
- Instituto de QuímicaUniversidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad UniversitariaMexico CityC.P. 04510Mexico
| | - Paola Sánchez‐Portillo
- Centro de Investigaciones Químicas-IICBAUniversidad Autónoma del Estado de MorelosAv. Universidad 1001Col. Chamilpa, Cuernavaca, MorelosC. P. 62209Mexico
| | - Lucero González‐Sebastián
- Universidad Autónoma Metropolitana-IztapalapaAv. San Rafael Atlixco No. 186Ciudad de MéxicoC.P. 09340México
| | - Arturo Sánchez‐Mora
- Instituto de QuímicaUniversidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad UniversitariaMexico CityC.P. 04510Mexico
| | - Brian Monroy‐Torres
- Instituto de QuímicaUniversidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad UniversitariaMexico CityC.P. 04510Mexico
| | - Teresa Ramírez‐Apan
- Instituto de QuímicaUniversidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad UniversitariaMexico CityC.P. 04510Mexico
| | - Nicolás Puentes‐Díaz
- Departamento de QuímicaUniversidad Nacional de Colombia- Sede BogotáBogotá111321Colombia
| | - Jorge Alí‐Torres
- Departamento de QuímicaUniversidad Nacional de Colombia- Sede BogotáBogotá111321Colombia
| | - Victor Barba
- Centro de Investigaciones Químicas-IICBAUniversidad Autónoma del Estado de MorelosAv. Universidad 1001Col. Chamilpa, Cuernavaca, MorelosC. P. 62209Mexico
| | - Viviana Reyes‐Marquez
- Departamento de Ciencias Químico-BiológicasUniversidad de SonoraLuis Encinas y Rosales s/nHermosillo, SonoraC.P. 83000Mexico
| | - David Morales‐Morales
- Instituto de QuímicaUniversidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad UniversitariaMexico CityC.P. 04510Mexico
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6
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You J, Shen J, Liu W, Zhou J, Yu Y, Liu C, Wang F, Li A, Qiao J. Biomimetic Nanoparticles for Targeted Lung Cancer Immunotherapy via Specific Clearance of High Potassium. ACS APPLIED NANO MATERIALS 2025; 8:3787-3803. [DOI: 10.1021/acsanm.4c06240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/03/2025]
Affiliation(s)
- Jiaqi You
- Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai 200011, China
| | - Jie Shen
- Department of Laboratory Medicine, Shanghai Tongji Hospital, School of medicine, School of life science and technology, Tongji University, No.1239 Siping Road, Shanghai 200065, China
| | - Wenwen Liu
- The Gynecology Department, Shanghai Key Laboratory of Maternal-Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine
- Tongji University
| | - Juan Zhou
- Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai 200011, China
| | - Yimin Yu
- Department of Laboratory Medicine, Shanghai Tongji Hospital, School of medicine, School of life science and technology, Tongji University, No.1239 Siping Road, Shanghai 200065, China
| | - Chengyu Liu
- Department of Laboratory Medicine, Shanghai Tongji Hospital, School of medicine, School of life science and technology, Tongji University, No.1239 Siping Road, Shanghai 200065, China
| | - Feng Wang
- Department of Thoracic Surgery, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai 200011, China
| | - Ang Li
- Department of Laboratory Medicine, Shanghai Tongji Hospital, School of medicine, School of life science and technology, Tongji University, No.1239 Siping Road, Shanghai 200065, China
| | - Jianou Qiao
- Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai 200011, China
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7
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Petkova V, Dobrev S, Kircheva N, Nazarova D, Nedelchev L, Nikolova V, Dudev T, Angelova S. Density Functional Theory Prediction of Laser Dyes-Cucurbit[7]uril Binding Affinities. Molecules 2024; 29:4394. [PMID: 39339389 PMCID: PMC11434600 DOI: 10.3390/molecules29184394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 09/08/2024] [Accepted: 09/14/2024] [Indexed: 09/30/2024] Open
Abstract
Among a variety of diverse host molecules distinguished by specific characteristics, the cucurbit[n]uril (CB) family stands out, being widely known for the attractive properties of its representatives along with their increasingly expanding area of applications. The presented herewith density functional theory (DFT)-based study is inspired by some recent studies exploring CBs as a key component in multifunctional hydrogels with applications in materials science, thus considering CB-assisted supramolecular polymeric hydrogels (CB-SPHs), a new class of 3D cross-linked polymer materials. The research systematically investigates the inclusion process between the most applied representative of the cavitand family CB[7] and a series of laser dye molecules as guests, as well as the possible encapsulation of a model side chain from the photoanisotropic polymer PAZO and its sodium-containing salt. The obtained results shed light on the most significant factors that play a key role in the recognition process, such as binding mode, charge, and dielectric constant of the solvent. The observed findings provide valuable insights at a molecular level for the design of dye-CB[7] systems in various environments, with potential applications in intriguing and prosperous fields like photonics and material science.
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Affiliation(s)
- Vladislava Petkova
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
| | - Stefan Dobrev
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
| | - Nikoleta Kircheva
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
| | - Dimana Nazarova
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
- University of Chemical Technology and Metallurgy, 8 St. Kliment Ohridski Blvd, 1756 Sofia, Bulgaria
| | - Lian Nedelchev
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
- University of Chemical Technology and Metallurgy, 8 St. Kliment Ohridski Blvd, 1756 Sofia, Bulgaria
| | - Valya Nikolova
- Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria; (V.N.); (T.D.)
| | - Todor Dudev
- Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria; (V.N.); (T.D.)
| | - Silvia Angelova
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (V.P.); (S.D.); (N.K.); (D.N.); (L.N.)
- University of Chemical Technology and Metallurgy, 8 St. Kliment Ohridski Blvd, 1756 Sofia, Bulgaria
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8
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Islamov II, Dzhemileva LU, Gaisin IV, Dzhemilev UM, D′yakonov VA. New Polyether Macrocycles as Promising Antitumor Agents-Targeted Synthesis and Induction of Mitochondrial Apoptosis. ACS OMEGA 2024; 9:19923-19931. [PMID: 38737069 PMCID: PMC11079895 DOI: 10.1021/acsomega.3c09566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/09/2024] [Accepted: 04/18/2024] [Indexed: 05/14/2024]
Abstract
A series of previously unknown aromatic polyether macrodiolides containing a cis,cis-1,5-diene moiety in the molecule were synthesized in 47-74% yields. Macrocycle compounds were first obtained by intermolecular esterification of aromatic polyether diols with α,ω-alka-nZ,(n+4)Z-dienedioic acids mediated by N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC·HCl) and 4-(dimethylamino)pyridine (DMAP). For the synthesized compounds, studies of cytotoxicity on tumor (Jurkat, K562, U937), conditionally normal (HEK293) cell lines, and normal fibroblasts were carried out. CC50 was determined, and the therapeutic selectivity index of cytotoxic action (SI) in comparison with normal fibroblasts was evaluated. With the involvement of modern methods of flow cytometry for the most promising macrocycles, their effect on mitochondria and the cell cycle was investigated. It was found that a new macrocycle exhibits pronounced apoptosis-inducing activity toward Jurkat cells and can retard cell division by blocking at the G1/S checkpoint. Also, it was shown that the synthesized macrodiolides influence mitochondria due to their high ability to penetrate the mitochondrial membrane.
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Affiliation(s)
- Ilgiz I. Islamov
- Institute
of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
| | - Lilya U. Dzhemileva
- N.
D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, Moscow 119991, Russian Federation
- State
Scientific Center of the Russian Federation Federal State Budgetary
Institution, “National Medical Research
Center of Endocrinology” of the Ministry of Health
of the Russian Federation, st. Dmitry Ulyanov, 11, Moscow 117292, Russian Federation
| | - Ilgam V. Gaisin
- Institute
of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
| | - Usein M. Dzhemilev
- N.
D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, Moscow 119991, Russian Federation
| | - Vladimir A. D′yakonov
- N.
D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, Moscow 119991, Russian Federation
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9
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Kim J, Kim S, Park J, Kang S, Seo DJ, Park N, Lee S, Kim JJ, Lee WB, Park J, Lee JC. Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality. J Am Chem Soc 2024; 146:4532-4541. [PMID: 38326951 DOI: 10.1021/jacs.3c11182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.
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Affiliation(s)
- Jinseok Kim
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Sungin Kim
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
| | - Jinwook Park
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Sungsu Kang
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
| | - Dong Joo Seo
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Namjun Park
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Siyoung Lee
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Jae Jun Kim
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Won Bo Lee
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Jungwon Park
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
- Institute of Engineering Research, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea
- Advanced Institutes of Convergence Technology, Seoul National University, Gyeonggi-do 16229, Republic of Korea
| | - Jong-Chan Lee
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
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10
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Mondal A, Siwach M, Ahmad M, Radhakrishnan SK, Talukdar P. Pyridyl-Linked Hetero Hydrazones: Transmembrane H +/Cl - Symporters with Efficient Antibacterial Activity. ACS Infect Dis 2024; 10:371-376. [PMID: 38262044 DOI: 10.1021/acsinfecdis.3c00455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2024]
Abstract
The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.
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11
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Kircheva N, Petkova V, Dobrev S, Nikolova V, Angelova S, Dudev T. N-Methyl- and N-Phenylpiperazine Functionalized Styryl Dyes Inside Cucurbiturils: Theoretical Assessment of the Factors Governing the Host-Guest Recognition. Molecules 2023; 28:8130. [PMID: 38138619 PMCID: PMC10746092 DOI: 10.3390/molecules28248130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 12/04/2023] [Accepted: 12/14/2023] [Indexed: 12/24/2023] Open
Abstract
The family of cucurbiturils (CBs), the unique pumpkin-shaped macrocycles, has received great attention over the past four decades owing to their remarkable recognition properties. They have found diverse applications including biosensing and drug delivery technologies. The cucurbituril complexation of guest molecules can modulate their pKas, improve their solubility in aqueous solution, and reduce the adverse effects of the drugs, as well as enhance the stability and/or enable targeted delivery of the drug molecule. Employing twelve cationic styryl dyes with N-methyl- and N-phenylpiperazine functionality as probes, we attempted to understand the factors that govern the host-guest complexation of such molecules within CB[7] and CB[8] host systems. Various key factors determining the process were recognized, such as the pH and dielectric constant of the medium, the cavity size of the host, the chemical characteristics of the substituents in the guest entity, and the presence/absence of metal cations. The presented results add to our understanding (at the molecular level) of the mechanism of encapsulation of styryl dyes by cucurbiturils, thus shedding new light on various aspects of the intriguing complexation chemistry and the underlying recognition processes.
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Affiliation(s)
- Nikoleta Kircheva
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (N.K.); (V.P.); (S.D.); (S.A.)
| | - Vladislava Petkova
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (N.K.); (V.P.); (S.D.); (S.A.)
| | - Stefan Dobrev
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (N.K.); (V.P.); (S.D.); (S.A.)
| | - Valya Nikolova
- Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria;
| | - Silvia Angelova
- Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria; (N.K.); (V.P.); (S.D.); (S.A.)
- University of Chemical Technology and Metallurgy, 8 St. Kliment Ohridski Blvd, 1756 Sofia, Bulgaria
| | - Todor Dudev
- Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria;
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12
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Hellwig H, Nowok A, Peksa P, Dulski M, Musioł R, Pawlus S, Kuś P. Molecular Dynamics and Near- Tg Phenomena of Cyclic Thioethers. Int J Mol Sci 2023; 24:17166. [PMID: 38138995 PMCID: PMC10742681 DOI: 10.3390/ijms242417166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/20/2023] [Accepted: 12/02/2023] [Indexed: 12/24/2023] Open
Abstract
This article presents the synthesis and molecular dynamics investigation of three novel cyclic thioethers: 2,3-(4'-methylbenzo)-1,4,7,10-tetrathiacyclododeca-2-ene (compound 1), 2,3,14,15-bis(4',4″(5″)-methylbenzo)-1,4,7,10,13,16,19,22,25-octathiacyclotetracosa-2,14-diene (compound 2), and 2,3,8,9-bis(4',4″(5″)-methylbenzo)-1,4,7,10-tetrathiacyclododeca-2,8-diene (compound 3). The compounds exhibit relatively high glass transition temperatures (Tg), which range between 254 and 283 K. This characteristic positions them within the so-far limited category of crown-like glass-formers. We demonstrate that cyclic thioethers may span both the realms of ordinary and sizeable molecular glass-formers, each featuring distinct physical properties. Furthermore, we show that the Tg follows a sublinear power law as a function of the molar mass within this class of compounds. We also reveal multiple dielectric relaxation processes of the novel cyclic thioethers. Above the Tg, their dielectric loss spectra are dominated by a structural relaxation, which originates from the cooperative reorientation of entire molecules and exhibits an excess wing on its high-frequency slope. This feature has been attributed to the Johari-Goldstein (JG) process. Each investigated compound exhibits also at least one intramolecular secondary non-JG relaxation stemming from conformational changes. Their activation energies range from approximately 19 kJ/mol to roughly 40 kJ/mol. Finally, we analyze the high-pressure molecular dynamics of compound 1, revealing a pressure-induced increase in its Tg with a dTg/dp coefficient equal to 197 ± 8 K/GPa.
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Affiliation(s)
- Hubert Hellwig
- Center for Integrated Technology and Organic Synthesis (CiTOS), MolSys Research Unit, University of Liège, B6a, Room 3/19, Allée du Six Août 13, 4000 Liege, Belgium;
| | - Andrzej Nowok
- Department of Experimental Physics, Wrocław University of Science and Technology, Wybrzeże Stanisława Wyspiańskiego 27, 50-370 Wrocław, Poland; (A.N.); (P.P.)
| | - Paulina Peksa
- Department of Experimental Physics, Wrocław University of Science and Technology, Wybrzeże Stanisława Wyspiańskiego 27, 50-370 Wrocław, Poland; (A.N.); (P.P.)
| | - Mateusz Dulski
- Faculty of Science and Technology, Institute of Materials Engineering, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500 Chorzów, Poland;
| | - Robert Musioł
- Institute of Chemistry, University of Silesia in Katowice, Szkolna 9, 40-003 Katowice, Poland;
| | - Sebastian Pawlus
- August Chełkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland;
| | - Piotr Kuś
- Institute of Chemistry, University of Silesia in Katowice, Szkolna 9, 40-003 Katowice, Poland;
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13
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Castillo-Pazos DJ, Lasso JD, Hamzehpoor E, Ramos-Sánchez J, Salgado JM, Cosa G, Perepichka DF, Li CJ. Triarylamines as catalytic donors in light-mediated electron donor–acceptor complexes. Chem Sci 2023; 14:3470-3481. [PMID: 37006691 PMCID: PMC10055340 DOI: 10.1039/d2sc07078b] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 02/12/2023] [Indexed: 03/16/2023] Open
Abstract
EDA complexes with catalytic triarylamines allow C–H perfluoroalkylation of arenes and heteroarenes under visible light irradiation in pH- and redox-neutral conditions. A detailed photophysical characterization of the EDA complex is provided.
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Affiliation(s)
- Durbis J. Castillo-Pazos
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
- FRQNT Centre for Green Chemistry and Catalysis, McGill University, Montreal, QC H3A 0B8, Canada
| | - Juan D. Lasso
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
- FRQNT Centre for Green Chemistry and Catalysis, McGill University, Montreal, QC H3A 0B8, Canada
| | - Ehsan Hamzehpoor
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
| | - Jorge Ramos-Sánchez
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
| | - Jan Michael Salgado
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
- FRQNT Centre for Green Chemistry and Catalysis, McGill University, Montreal, QC H3A 0B8, Canada
| | - Gonzalo Cosa
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
- FRQNT Centre for Green Chemistry and Catalysis, McGill University, Montreal, QC H3A 0B8, Canada
| | - Dmytro F. Perepichka
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
| | - Chao-Jun Li
- Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada
- FRQNT Centre for Green Chemistry and Catalysis, McGill University, Montreal, QC H3A 0B8, Canada
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14
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Host-Guest Complexes. Int J Mol Sci 2022; 23:ijms232415730. [PMID: 36555372 PMCID: PMC9779678 DOI: 10.3390/ijms232415730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/14/2022] Open
Abstract
Host-guest complexes, also known as inclusion complexes, are supramolecular structures [...].
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15
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Lucio-Martínez F, Reigosa F, Bermúdez B, Adams H, Pereira MT, Vila JM. Cyclometallated Platinum(II) Complexes with Small Crown Ether Rings: Appropriate Choice of the Bridging Diphosphane to Coordinate Potassium Cations. ACS OMEGA 2022; 7:37256-37263. [PMID: 36312351 PMCID: PMC9609057 DOI: 10.1021/acsomega.2c03526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/14/2022] [Indexed: 06/16/2023]
Abstract
This account reports the synthesis and structural characterization of the first cyclometallated platinum(II) complex that coordinates a potassium cation in a sandwich arrangement via two 15-crown-5 ether rings within the same molecule. The cooperation of the two small crown ether moieties allows the entrapment of the non-ideal potassium ion. The reaction of the parent thiosemicarbazone ligand 3,4-(C8H16O5)C6H3C(Me)=NN-(H)C(=S)NHMe, 1, containing the crown ether ring, with K2[PtCl4], or alternatively with PtCl2(DMSO)2, and subsequent treatment with the diphosphanes Ph2PCH2PPh2 (dppm) and Ph2PC(=CH2)PPh2 (vdpp) produced the double nuclear platinacycles 3a, 3b, and 4, probably via formation of the 2a and 2b intermediates. Complex 3a with the K+ cation in a sandwich coordination was slightly mixed with 3b lacking any K+. Alternatively, reaction of 1 with K2[PtCl4] or with PtCl2(DMSO)2 followed by the diphosphane Ph2PC(=CH2)PPh2 (vdpp) only gave the dinuclear phosphane-bridged compound 4; this highlights the importance of choosing the right diphosphane ligand. Density functional theory calculations (B3LYP-D3/LANL2DZ-ECP-6.311++G**) revealed similar affinities for both dppm and vdpp derivatives to coordinate potassium cations. Crystal structure analysis was performed for compounds 3a and 4.
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Affiliation(s)
- Fátima Lucio-Martínez
- Department
of Inorganic Chemistry, University of Santiago
de Compostela, Santiago de Compostela E-15782, Spain
| | - Francisco Reigosa
- Department
of Inorganic Chemistry, University of Santiago
de Compostela, Santiago de Compostela E-15782, Spain
| | - Brais Bermúdez
- Department
of Inorganic Chemistry, University of Santiago
de Compostela, Santiago de Compostela E-15782, Spain
| | - Harry Adams
- Department
of Chemistry, The University of Sheffield, Sheffield S3 7HF, U.K.
| | - M. Teresa Pereira
- Department
of Inorganic Chemistry, University of Santiago
de Compostela, Santiago de Compostela E-15782, Spain
| | - José M. Vila
- Department
of Inorganic Chemistry, University of Santiago
de Compostela, Santiago de Compostela E-15782, Spain
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16
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Al-Saidi HM, Khan S. A Review on Organic Fluorimetric and Colorimetric Chemosensors for the Detection of Ag(I) Ions. Crit Rev Anal Chem 2022; 54:1810-1836. [PMID: 36251012 DOI: 10.1080/10408347.2022.2133561] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Organic compounds display several electronic and structural features which enable their application in various fields, ranging from biological to non-biological. These compounds contain heteroatoms like sulfur, nitrogen and oxygen, which provide coordination sites to act as ligands in the field of coordination chemistry and are used as chemosensors to detect various metal ions. This review article covers different organic compounds including thiourea, Schiff base, pyridine, thiophene, coumarin, triazolyl pyrenes, imidazole, fluorescein, thiazole, tricarbocyanine, rhodanine, porphyrin, hydrazone, benzidine and other functional groups based chemosensors, that contain heteroatoms like sulfur, nitrogen and, oxygen for fluorimetric and colorimetric detection of Ag+ in different environmental, agricultural, and biological samples. Further, the sensing mechanism and performances of these chemosensors have been discussed, which could help the readers for the future design of highly efficient, selective, and sensitive chemosensors for the detection and determination of Ag+ ions.
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Affiliation(s)
- Hamed M Al-Saidi
- Department of Chemistry, University College in Al-Jamoum, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Sikandar Khan
- Department of Chemistry, University of Malakand, Khyber Pakhtunkhwa, Pakistan
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17
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Ullah F, Ullah S, Khan MFA, Mustaqeem M, Paracha RN, Rehman MFU, Kanwal F, Hassan SSU, Bungau S. Fluorescent and Phosphorescent Nitrogen-Containing Heterocycles and Crown Ethers: Biological and Pharmaceutical Applications. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196631. [PMID: 36235167 PMCID: PMC9573242 DOI: 10.3390/molecules27196631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/01/2022] [Accepted: 10/03/2022] [Indexed: 11/29/2022]
Abstract
Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy.
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Affiliation(s)
- Faiz Ullah
- Department of Chemistry, Quaid I Azam University, Islamabad 45320, Pakistan
- Correspondence: (F.U.); (S.S.u.H.); (S.B.)
| | - Sami Ullah
- Department of Zoology, Government College University, Faisalabad 38000, Pakistan
| | - Muhammad Farhan Ali Khan
- Faculty of Pharmacy, Capital University of Science and Technology, Islamabad Expressway, Islamabad 44000, Pakistan
| | - Muhammad Mustaqeem
- Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan
| | - Rizwan Nasir Paracha
- Department of Chemistry, Sub Campus, University of Sargodha, Bhakkar 30000, Pakistan
| | | | - Fariha Kanwal
- School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai 200030, China
| | - Syed Shams ul Hassan
- Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
- Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
- Correspondence: (F.U.); (S.S.u.H.); (S.B.)
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Correspondence: (F.U.); (S.S.u.H.); (S.B.)
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18
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Algethami JS. A Review on Recent Progress in Organic Fluorimetric and Colorimetric Chemosensors for the Detection of Cr 3+/6+Ions. Crit Rev Anal Chem 2022; 54:487-507. [PMID: 35758232 DOI: 10.1080/10408347.2022.2082242] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Chromium occurs in the environment primarily in two valence states, trivalent Cr3+ and hexavalent Cr6+, which have different physicochemical and biochemical properties. However, the higher concentration of Cr3+/6+ can cause various adverse effects on human health. Therefore, detecting Cr3+/6+ ions is important in various samples. Colorimetric and fluorescent chemosensors are the most powerful tools for the detection of Cr3+/6+ ions. These chemosensors have excellent bioimaging capability and significant sensitivity and selectivity. In this article, different colorimetric and fluorescent chemosensors based on organic compounds, including Schiff base, antipyrine, diarylethene, pyrene, crown ether, dansyl, pyridine, thiazole, coumarin, boradiazaindacene, rhodamine, imidazole, hydrazone, and other functional groups for detection of Cr3+/6+ ions have been reviewed, classified them according to different fluorophore and recognition mode. I hope this article will help the readers for the future design of highly effective, sensitive, and selective chemosensors for the detection and determination of Cr3+/6+ ions.
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Affiliation(s)
- Jari S Algethami
- Department of Chemistry, College of Science and Arts, Najran University, Najran, Saudi Arabia
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19
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Interaction of crown ethers with the ABCG2 transporter and their implication for multidrug resistance reversal. Histochem Cell Biol 2022; 158:261-277. [PMID: 35648291 DOI: 10.1007/s00418-022-02106-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2022] [Indexed: 02/03/2023]
Abstract
Overexpression of ABC transporters, such as ABCB1 and ABCG2, plays an important role in mediating multidrug resistance (MDR) in cancer. This feature is also attributed to a subpopulation of cancer stem cells (CSCs), having enhanced tumourigenic potential. ABCG2 is specifically associated with the CSC phenotype, making it a valuable target for eliminating aggressive and resistant cells. Several natural and synthetic ionophores have been discovered as CSC-selective drugs that may also have MDR-reversing ability, whereas their interaction with ABCG2 has not yet been explored. We previously reported the biological activities, including ABCB1 inhibition, of a group of adamantane-substituted diaza-18-crown-6 (DAC) compounds that possess ionophore capabilities. In this study, we investigated the mechanism of ABCG2-inhibitory activity of DAC compounds and the natural ionophores salinomycin, monensin and nigericin. We used a series of functional assays, including real-time microscopic analysis of ABCG2-mediated fluorescent substrate transport in cells, and docking studies to provide comparative aspects for the transporter-compound interactions and their role in restoring chemosensitivity. We found that natural ionophores did not inhibit ABCG2, suggesting that their CSC selectivity is likely mediated by other mechanisms. In contrast, DACs with amide linkage in the side arms demonstrated noteworthy ABCG2-inhibitory activity, with DAC-3Amide proving to be the most potent. This compound induced conformational changes of the transporter and likely binds to both Cavity 1 and the NBD-TMD interface. DAC-3Amide reversed ABCG2-mediated MDR in model cells, without affecting ABCG2 expression or localization. These results pave the way for the development of new crown ether compounds with improved ABCG2-inhibitory properties.
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20
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Saji VS. Recent Updates on Supramolecular-Based Drug Delivery - Macrocycles and Supramolecular Gels. CHEM REC 2022; 22:e202200053. [PMID: 35510981 DOI: 10.1002/tcr.202200053] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/05/2022] [Indexed: 11/09/2022]
Abstract
Supramolecules-based drug delivery has attracted significant recent research attention as it could enhance drug solubility, retention time, targeting, and stimuli responsiveness. Among the different supramolecules and assemblies, the macrocycles and the supramolecular hydrogels are the two important categories investigated to a greater extent. Here, we provide the most recent advancements in these categories. Under macrocycles, reports on drug delivery by cyclodextrins, cucurbiturils, calixarenes/pillararenes, crown ethers and porphyrins are detailed. The second category discusses the supramolecular hydrogels of macrocycles/polymers and low molecular weight gelators. The updated information provided could be helpful to advance R & D in this vital area.
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Affiliation(s)
- Viswanathan S Saji
- Interdisciplinary Research Center for Advanced Materials, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia
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21
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Molecular Recognition by Pillar[5]arenes: Evidence for Simultaneous Electrostatic and Hydrophobic Interactions. Pharmaceutics 2021; 14:pharmaceutics14010060. [PMID: 35056956 PMCID: PMC8777861 DOI: 10.3390/pharmaceutics14010060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/17/2021] [Accepted: 12/22/2021] [Indexed: 11/21/2022] Open
Abstract
The formation of inclusion complexes between alkylsulfonate guests and a cationic pillar[5]arene receptor in water was investigated by NMR and ITC techniques. The results show the formation of host-guest complexes stabilized by electrostatic interactions and hydrophobic effects with binding constants of up to 107 M−1 for the guest with higher hydrophobic character. Structurally, the alkyl chain of the guest is included in the hydrophobic aromatic cavity of the macrocycle while the sulfonate groups are held in the multicationic portal by ionic interactions.
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22
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Park SH, Hwang I, McNaughton DA, Kinross AJ, Howe EN, He Q, Xiong S, Kilde MD, Lynch VM, Gale PA, Sessler JL, Shin I. Synthetic Na +/K + exchangers promote apoptosis by disturbing cellular cation homeostasis. Chem 2021; 7:3325-3339. [PMID: 38239771 PMCID: PMC10795848 DOI: 10.1016/j.chempr.2021.08.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A number of artificial cation ionophores (or transporters) have been developed for basic research and biomedical applications. However, their mechanisms of action and the putative correlations between changes in intracellular cation concentrations and induced cell death remain poorly understood. Here, we show that three hemispherand-strapped calix[4]pyrrole-based ion-pair receptors act as efficient Na+/K+ exchangers in the presence of Cl- in liposomal models and promote Na+ influx and K+ efflux (Na+/K+ exchange) in cancer cells to induce apoptosis. Mechanistic studies reveal that these cation exchangers induce endoplasmic reticulum (ER) stress in cancer cells by perturbing intracellular cation homeostasis, promote generation of reactive oxygen species, and eventually enhance mitochondria-mediated apoptosis. However, they neither induce osmotic stress nor affect autophagy. This study provides support for the notion that synthetic receptors, which perturb cellular cation homeostasis, may provide new small molecules with potentially useful apoptotic activity.
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Affiliation(s)
- Sang-Hyun Park
- Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
- These authors contributed equally
| | - Inhong Hwang
- Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Stop A5300, Austin, TX 78712, USA
- These authors contributed equally
| | - Daniel A. McNaughton
- School of Chemistry (F11), The University of Sydney, Sydney, NSW 2006, Australia
- These authors contributed equally
| | - Airlie J. Kinross
- School of Chemistry (F11), The University of Sydney, Sydney, NSW 2006, Australia
| | - Ethan N.W. Howe
- School of Chemistry (F11), The University of Sydney, Sydney, NSW 2006, Australia
- Present address: GlaxoSmithKline, GSK Jurong, 1 Pioneer Sector 1, Singapore 628413
| | - Qing He
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P.R. China
| | - Shenglun Xiong
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P.R. China
| | - Martin Drøhse Kilde
- Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Stop A5300, Austin, TX 78712, USA
- Present address: Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark
| | - Vincent M. Lynch
- Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Stop A5300, Austin, TX 78712, USA
| | - Philip A. Gale
- School of Chemistry (F11), The University of Sydney, Sydney, NSW 2006, Australia
- The University of Sydney Nano Institute (SydneyNano), The University of Sydney, Sydney, NSW 2006, Australia
| | - Jonathan L. Sessler
- Department of Chemistry, The University of Texas at Austin, 105 East 24th Street, Stop A5300, Austin, TX 78712, USA
- Lead contact
| | - Injae Shin
- Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea
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23
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Abstract
Artificial receptors able to recognise biologically relevant molecules or ions have gained interest in the chemical community because they offer a plethora of posibilities. Molecular cage compounds are polycyclic compounds with a cavity designed for the encapsulation of guest species. Once inside the host cavity, the substrate can be transported through membranes and protected from the action of enzymes or other reactive species, thus offering the possibility of interfering with biological systems. Commonly, enzymes have been an inspiration for chemists in the search and design of defined cavities for different purposes. However, the chemical preparation of molecular cages has struggled with many synthetic challenges but this effort is worthwhile as they are a very promising tool for many applications ranging from sensing, delivery, purification or even promotion of/prevention from chemical modifications. Since the early reports at the end of the 60s, this field has experienced a growing interest; this review summarises the progress in the preparation and study of cage-like compounds highlighting their importance in biological applications.
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Affiliation(s)
- Lucía Tapia
- Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
| | - Ignacio Alfonso
- Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
| | - Jordi Solà
- Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain.
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Dao NT, Nguyen DT, Nguyen LM, Tran VTT, Do TT, Le AT. Synthesis of Dithiacrown Ethers and Evaluation of Their Cytotoxic Activity. ChemistrySelect 2021. [DOI: 10.1002/slct.202102963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- N. T. Dao
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
| | - D. T. Nguyen
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
| | - L. M. Nguyen
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
- Faculty of Pharmacy Thai Nguyen University of Medicine and Pharmacy 284 Luong Ngoc Quyen Street Thai Nguyen Vietnam
| | - V. T. T. Tran
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
| | - T. T. Do
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
| | - A. T. Le
- Faculty of Chemistry, VNU University of Science Vietnam National University Hanoi 334 Nguyen Trai Street, Thanh Xuan, Ha Noi 100000 Vietnam
- Faculty of Agricultural Technology VNU University of Engineering and Technology 144 Xuan Thuy Cau Giay, Hanoi 100000 Vietnam
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Abstract
Several life-threatening diseases, also known as 'Channelopathies' are linked to irregularities in ion transport proteins. Significant research efforts have fostered the development of artificial transport systems that facilitates to restore the functions of impaired natural transport proteins. Indeed, a few of these artificial ionophores demonstrate the rare combination of transmembrane ion transport and important biological activity, offering early promises of suitability in 'channel replacement therapy'. In this review, structural facets and functions of both cationophores and anionophores are discussed. Ionophores that are toxic to various bacteria and yeast, could be exploited as antimicrobial agent. Nevertheless, few non-toxic ionophores offer the likelihood of treating a wide range of genetic diseases caused by the gene mutations. In addition, their ability to disrupt cellular homeostasis and to alter lysosomal pH endow ionophores as promising candidates for cancer treatment. Overall, critically outlining the advances in artificial ionophores in terms of in vitro ion transport, possible modes of action and biological activities enables us to propose possible future roadmaps in this research area.
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Affiliation(s)
- Arundhati Roy
- Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377, Munich, Germany
| | - Pinaki Talukdar
- Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune, 411008, India
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26
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Koçoğlu S, Hayvalı Z, Ogutcu H. A polydentate ligand based on 2,2’-dipyridylamine unit linked benzo-15-crown-5; alkali and transition metal complexes; photoresponsive ligand; antimicrobial evaluation against pathogenic microorganisms. TRANSIT METAL CHEM 2021. [DOI: 10.1007/s11243-021-00469-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Herschede SR, Gneid H, Dent T, Jaeger EB, Lawson LB, Busschaert N. Bactericidal urea crown ethers target phosphatidylethanolamine membrane lipids. Org Biomol Chem 2021; 19:3838-3843. [PMID: 33949594 DOI: 10.1039/d1ob00263e] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
An increasing number of people are infected with antibiotic-resistant bacteria each year, sometimes with fatal consequences. In this manuscript, we report a novel urea-functionalized crown ether that can bind to the bacterial lipid phosphatidylethanolamine (PE), facilitate PE flip-flop and displays antibacterial activity against the Gram-positive bacterium Bacillus cereus with a minimum inhibitory concentration comparable to that of the known PE-targeting lantibiotic duramycin.
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Affiliation(s)
- Sarah R Herschede
- Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
| | - Hassan Gneid
- Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
| | - Taylor Dent
- Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
| | - Ellen B Jaeger
- Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
| | - Louise B Lawson
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA
| | - Nathalie Busschaert
- Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA.
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28
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Basok SS, Schepetkin IA, Khlebnikov AI, Lutsyuk AF, Kirichenko TI, Kirpotina LN, Pavlovsky VI, Leonov KA, Vishenkova DA, Quinn MT. Synthesis, Biological Evaluation, and Molecular Modeling of Aza-Crown Ethers. Molecules 2021; 26:molecules26082225. [PMID: 33921479 PMCID: PMC8069214 DOI: 10.3390/molecules26082225] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/04/2021] [Accepted: 04/07/2021] [Indexed: 11/16/2022] Open
Abstract
Synthetic and natural ionophores have been developed to catalyze ion transport and have been shown to exhibit a variety of biological effects. We synthesized 24 aza- and diaza-crown ethers containing adamantyl, adamantylalkyl, aminomethylbenzoyl, and ε-aminocaproyl substituents and analyzed their biological effects in vitro. Ten of the compounds (8, 10–17, and 21) increased intracellular calcium ([Ca2+]i) in human neutrophils, with the most potent being compound 15 (N,N’-bis[2-(1-adamantyl)acetyl]-4,10-diaza-15-crown-5), suggesting that these compounds could alter normal neutrophil [Ca2+]i flux. Indeed, a number of these compounds (i.e., 8, 10–17, and 21) inhibited [Ca2+]i flux in human neutrophils activated by N-formyl peptide (fMLF). Some of these compounds also inhibited chemotactic peptide-induced [Ca2+]i flux in HL60 cells transfected with N-formyl peptide receptor 1 or 2 (FPR1 or FPR2). In addition, several of the active compounds inhibited neutrophil reactive oxygen species production induced by phorbol 12-myristate 13-acetate (PMA) and neutrophil chemotaxis toward fMLF, as both of these processes are highly dependent on regulated [Ca2+]i flux. Quantum chemical calculations were performed on five structure-related diaza-crown ethers and their complexes with Ca2+, Na+, and K+ to obtain a set of molecular electronic properties and to correlate these properties with biological activity. According to density-functional theory (DFT) modeling, Ca2+ ions were more effectively bound by these compounds versus Na+ and K+. The DFT-optimized structures of the ligand-Ca2+ complexes and quantitative structure-activity relationship (QSAR) analysis showed that the carbonyl oxygen atoms of the N,N’-diacylated diaza-crown ethers participated in cation binding and could play an important role in Ca2+ transfer. Thus, our modeling experiments provide a molecular basis to explain at least part of the ionophore mechanism of biological action of aza-crown ethers.
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Affiliation(s)
- Stepan S. Basok
- A.V. Bogatsky Physico-Chemical Institute of National Academy of Science of Ukraine, 65080 Odessa, Ukraine; (S.S.B.); (A.F.L.); (T.I.K.)
| | - Igor A. Schepetkin
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (I.A.S.); (L.N.K.)
| | - Andrei I. Khlebnikov
- Kizhner Research Center, National Research Tomsk Polytechnic University, Tomsk 634050, Russia; (A.I.K.); (V.I.P.); (D.A.V.)
| | - Anatoliy F. Lutsyuk
- A.V. Bogatsky Physico-Chemical Institute of National Academy of Science of Ukraine, 65080 Odessa, Ukraine; (S.S.B.); (A.F.L.); (T.I.K.)
| | - Tatiana I. Kirichenko
- A.V. Bogatsky Physico-Chemical Institute of National Academy of Science of Ukraine, 65080 Odessa, Ukraine; (S.S.B.); (A.F.L.); (T.I.K.)
| | - Liliya N. Kirpotina
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (I.A.S.); (L.N.K.)
| | - Victor I. Pavlovsky
- Kizhner Research Center, National Research Tomsk Polytechnic University, Tomsk 634050, Russia; (A.I.K.); (V.I.P.); (D.A.V.)
- Innovative Pharmacology Research, LLC, Tomsk 634021, Russia;
| | - Klim A. Leonov
- Innovative Pharmacology Research, LLC, Tomsk 634021, Russia;
| | - Darya A. Vishenkova
- Kizhner Research Center, National Research Tomsk Polytechnic University, Tomsk 634050, Russia; (A.I.K.); (V.I.P.); (D.A.V.)
| | - Mark T. Quinn
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (I.A.S.); (L.N.K.)
- Correspondence: ; Tel.: +406-994-4707; Fax: +406-994-4303
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Vázquez-González M, Zhou Z, Biniuri Y, Willner B, Willner I. Mimicking Functions of Native Enzymes or Photosynthetic Reaction Centers by Nucleoapzymes and Photonucleoapzymes. Biochemistry 2021; 60:956-965. [PMID: 32613829 PMCID: PMC8028052 DOI: 10.1021/acs.biochem.0c00421] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/02/2020] [Indexed: 11/29/2022]
Abstract
The covalent linkage of catalytic units to aptamer sequence-specific nucleic acids exhibiting selective binding affinities for substrates leads to functional scaffolds mimicking native enzymes, nucleoapzymes. The binding of the substrates to the aptamer and their structural orientation with respect to the catalytic units duplicate the functions of the active center of enzymes. The possibility of linking the catalytic sites directly, or through spacer units, to the 5'-end, 3'-end, and middle positions of the aptamers allows the design of nucleoapzyme libraries, revealing structure-functions diversities, and these can be modeled by molecular dynamics simulations. Catalytic sites integrated into nucleoapzymes include DNAzymes, transition metal complexes, and organic ligands. Catalytic transformations driven by nucleoapzymes are exemplified by the oxidation of dopamine or l-arginine, hydroxylation of tyrosine to l-DOPA, hydrolysis of ATP, and cholic acid-modified esters. The covalent linkage of photosensitizers to the tyrosinamide aptamer leads to a photonucleoapzyme scaffold that binds the N-methyl-N'-(3-aminopropane)-4,4'-bipyridinium-functionalized tyrosinamide to the aptamer. By linking the photosensitizer directly, or through a spacer bridge to the 5'-end or 3'-end of the aptamer, we demonstrate a library of supramolecular photosensitizer/electron acceptor photonucleoapzymes mimicking the functions of photosystem I in the photosynthetic apparatus. The photonucleoapzymes catalyze the photoinduced generation of NADPH, in the presence of ferredoxin-NADP+-reductase (FNR), or the photoinduced H2 evolution catalyzed by Pt nanoparticles. The future prospects of nucleoapzymes and photonucleoapzymes are discussed.
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Affiliation(s)
- Margarita Vázquez-González
- Institute of Chemistry, The Minerva
Center of Biohybrid Complex Systems, The
Hebrew University of Jerusalem, Jerusalem 91904, Israel
| | - Zhixin Zhou
- Institute of Chemistry, The Minerva
Center of Biohybrid Complex Systems, The
Hebrew University of Jerusalem, Jerusalem 91904, Israel
| | - Yonatan Biniuri
- Institute of Chemistry, The Minerva
Center of Biohybrid Complex Systems, The
Hebrew University of Jerusalem, Jerusalem 91904, Israel
| | - Bilha Willner
- Institute of Chemistry, The Minerva
Center of Biohybrid Complex Systems, The
Hebrew University of Jerusalem, Jerusalem 91904, Israel
| | - Itamar Willner
- Institute of Chemistry, The Minerva
Center of Biohybrid Complex Systems, The
Hebrew University of Jerusalem, Jerusalem 91904, Israel
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30
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Arenaza-Corona A, Couce-Fortúnez MD, de Blas A, Morales-Morales D, Santillan R, Höpfl H, Rodríguez-Blas T, Barba V. Further Approaches in the Design of Antitumor Agents with Response to Cell Resistance: Looking toward Aza Crown Ether-dtc Complexes. Inorg Chem 2020; 59:15120-15134. [PMID: 33000942 DOI: 10.1021/acs.inorgchem.0c02068] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The dianionic aza crown ether-dtc N,N'-bis(dithiocarbamate)-1,10-diaza-18-crown-6 (L2-) is a versatile ligand capable of yielding binuclear complexes with group 10 elements, also known as Ni-triade, [μ-(κ2-S,-S'-L)M2(PPh3)4]Cl2 (M = Pd (1), Pt (2)), [μ-(κ2-S,-S'-L)M2(PPh3)4](BPh4)2 (M = Pd (3), Pt (4)), and μ-(κ-S,-S'-L)Ni2(PPh3)2Cl2 (5), and has proven to be an excellent option to the design of metal-based drugs able to provide multiple response to cell resistance. Palladium and platinum complexes, 1 and 2, were tested for cytotoxicity in the human cervix carcinoma cell line HeLa-229, the human ovarian carcinoma cell line A2780, and the cisplatin-resistant mutant A2780cis, finding significant activity toward all three cancer cell lines, with low micromolar IC50 values, comparable to cisplatin. Markedly, against the cisplatin resistant cell line A2780cis, compound 2 exhibits better cytotoxic activity than the clinical drug (IC50 = 2.3 ± 0.2 μM for 2 versus 3.6 ± 0.5 μM for cisplatin). Moreover, an enhancement of the antitumor response is achieved when adding an equimolar amount of alkali metal chloride (NaCl or KCl) to the medium, for instance, testing compound 1 against the cisplatin-resistant A2780cis cells, the IC50 decreases from 9.3 ± 0.4 to 7.4 ± 0.3 and 5.4 ± 0.1 μM, respectively, after addition of the salt solution. For the platinum derivative 2, the IC50 improves by ca. 40% reaching 1.3 ± 0.1 μM when potassium chloride is added. Likewise, the resistant factor found for 2 (RF = 1) confirms that this complex circumvents cisplatin-resistance in A2780cis and is improved with the addition of potassium chloride (RF = 0.65). The presence of the aza crown ether moiety as linker in the systems studied herein is a key point since, in addition to allowing and facilitating interaction with alkali metal ions, this unit is flexible enough to adapt to a variety of environments, as confirmed by the X-ray crystal structures described, where different conformations and ways to fold in are found. In order to gain insight into the electronic and structural facts involved in the interaction of complex 2 with the alkali metal ions, a DFT study was performed, and the description of the molecular electrostatic potentials (MEPs) is also presented.
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Affiliation(s)
- Antonino Arenaza-Corona
- Grupo METMED, Departamento de Quı́mica & Centro de Investigaciones Cientı́ficas Avanzadas (CICA), Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain.,Centro de Investigaciones Quı́micas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, C.P., 62209 Cuernavaca, Morelos, Mexico
| | - M Delfina Couce-Fortúnez
- Departamento de Quı́mica Inorgánica, Instituto de Investigación Sanitaria Galicia Sur, Facultade de Quı́mica, Universidad de Vigo, 36310 Vigo, Spain
| | - Andrés de Blas
- Grupo METMED, Departamento de Quı́mica & Centro de Investigaciones Cientı́ficas Avanzadas (CICA), Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain
| | - David Morales-Morales
- Instituto de Quı́mica, Universidad Nacional Autónoma de México, Cd. Universitaria, Circuito Exterior, Coyoacán, 04510 Ciudad de México, Mexico
| | - Rosa Santillan
- Departamento de Quı́mica, Centro de Investigación y de Estudios Avanzados del IPN, 07000 Ciudad de México, Mexico
| | - Herbert Höpfl
- Centro de Investigaciones Quı́micas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, C.P., 62209 Cuernavaca, Morelos, Mexico
| | - Teresa Rodríguez-Blas
- Grupo METMED, Departamento de Quı́mica & Centro de Investigaciones Cientı́ficas Avanzadas (CICA), Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain
| | - Victor Barba
- Centro de Investigaciones Quı́micas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, C.P., 62209 Cuernavaca, Morelos, Mexico
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31
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Kircheva N, Dobrev S, Dasheva L, Koleva I, Nikolova V, Angelova S, Dudev T. Complexation of biologically essential (mono- and divalent) metal cations to cucurbiturils: a DFT/SMD evaluation of the key factors governing the host-guest recognition. RSC Adv 2020; 10:28139-28147. [PMID: 35519129 PMCID: PMC9055741 DOI: 10.1039/d0ra04387g] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/20/2020] [Indexed: 01/31/2023] Open
Abstract
Supramolecular complexes based on classical synthetic macrocyclic host molecules such as cyclodextrins and calixarenes have received much attention recently due to their broad applications as biological and chemical sensors, bioimaging agents, drug delivery carriers, light-emitting materials, etc. Cucurbit[n]urils comprise another group of cavitands known for their high affinity for various guest molecules. Nonetheless, some aspects of their coordination chemistry remain enigmatic. Although they are recognized as potential biomimetic scaffolds, they are still not tested as metalloenzyme models and not much is known about their metal-binding properties. Furthermore, there is no systematic study on the key factors controlling the processes of metal coordination to these systems. In the computational study herein, DFT molecular modeling has been employed in order to investigate the interactions of biologically essential (mono- and divalent) metal cations to cucurbit[n]urils and evaluate the major determinants shaping the process. The thermodynamic descriptors (Gibbs energies in the gas phase and in a water medium) of the corresponding complexation reactions have been estimated. The results obtained shed light on the mechanism of host-guest recognition and disclose which factors more specifically affect the metal binding process.
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Affiliation(s)
- Nikoleta Kircheva
- Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences 1113 Sofia Bulgaria
| | - Stefan Dobrev
- Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences 1113 Sofia Bulgaria
| | - Lyubima Dasheva
- Faculty of Chemistry and Pharmacy, Sofia University "St. Kl. Ohridski" 1164 Sofia Bulgaria
| | - Iskra Koleva
- Faculty of Chemistry and Pharmacy, Sofia University "St. Kl. Ohridski" 1164 Sofia Bulgaria
| | - Valya Nikolova
- Faculty of Chemistry and Pharmacy, Sofia University "St. Kl. Ohridski" 1164 Sofia Bulgaria
| | - Silvia Angelova
- Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences 1113 Sofia Bulgaria
| | - Todor Dudev
- Faculty of Chemistry and Pharmacy, Sofia University "St. Kl. Ohridski" 1164 Sofia Bulgaria
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Zubenko AD, Fedorova OA. Aromatic and heteroaromatic azacrown compounds: advantages and disadvantages of rigid macrocyclic ligands. RUSSIAN CHEMICAL REVIEWS 2020. [DOI: 10.1070/rcr4913] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Current approaches to the synthesis of aromatic and heteroaromatic azamacrocycles and their derivatives are summarized and systematized. The relationship between the structure of azacrown compounds and their complexation behaviour towards metal cations is analyzed. The diversity of practical applications of azamacrocyclic derivatives in medicine, biology and analytical and organic chemistry, as well as for the design of molecular devices is demonstrated.
The bibliography includes 307 references.
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Şener Cemaloğlu Ö, Ogutcu H, Hayvalı Z. Synthesis, characterization, and antimicrobial activities of novel double-armed benzo-15-crown-5 and their sodium and potassium complexes. JOURNAL OF CHEMICAL RESEARCH 2020. [DOI: 10.1177/1747519820932264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
New aldehyde- and halogen- (Cl, Br, I) substituted double-armed benzo-15-crown-5 derivatives are synthesized by the reactions of 4′,5′-bis(bromomethyl)benzo-15-crown-5 with 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde, or 5-iodosalicylaldehyde. The sodium and potassium complexes are obtained by reaction of crown ether with sodium perchlorate and potassium iodide, respectively. Novel Schiff base compounds containing three groups of benzo-15-crown-5 are obtained from the condensation of aldehydes with 4′-aminobenzo-15-crown-5. The structures of all compounds are elucidated by elemental analysis, 1H, 13C NMR, IR, and mass spectra. The antifungal and antibacterial effects of the synthesized ligands are evaluated against pathogenic microorganisms and show varying degrees of inhibitory effects against the growth of different pathogenic strains. Graphical abstract
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Affiliation(s)
- Öznur Şener Cemaloğlu
- Department of Chemistry, Faculty of Science, Ankara University, Ankara, Turkey
- Department of Chemistry, Faculty of Science, Akdeniz University, Antalya, Turkey
| | - Hatice Ogutcu
- Department of Field Crops, Faculty of Agriculture, Ahi Evran University, Kırşehir, Turkey
| | - Zeliha Hayvalı
- Department of Chemistry, Faculty of Science, Ankara University, Ankara, Turkey
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Thermodynamics of amine mixtures. Systems formed by alkyl-amine and ether, or N,N-dialkylamide, or ethanenitrile. J Mol Liq 2020. [DOI: 10.1016/j.molliq.2020.112907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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35
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Erkuş B, Özcan H, Zaim Ö. Synthesis, antimicrobial activity, and ion transportation investigation of four new [1 + 1] condensed furan and thiophene‐based cycloheterophane amides. J Heterocycl Chem 2020. [DOI: 10.1002/jhet.3922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Betül Erkuş
- Department of ChemistryTrakya University Edirne Turkey
| | - Hafize Özcan
- Department of ChemistryTrakya University Edirne Turkey
| | - Ömer Zaim
- Department of ChemistryTrakya University Edirne Turkey
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36
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Schneider T, Brüssow N, Yuvanc A, Budisa N. Synthesis of New Aza‐ and Thia‐Crown Ether Based Amino Acids. ChemistrySelect 2020. [DOI: 10.1002/slct.202000122] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Tobias Schneider
- Institute of ChemistryTechnical University of Berlin Müller-Breslau-Str. 10 Berlin 10623 Germany
| | - Nico Brüssow
- Institute of ChemistryTechnical University of Berlin Müller-Breslau-Str. 10 Berlin 10623 Germany
| | - Alev Yuvanc
- Institute of ChemistryTechnical University of Berlin Müller-Breslau-Str. 10 Berlin 10623 Germany
| | - Nediljko Budisa
- Institute of ChemistryTechnical University of Berlin Müller-Breslau-Str. 10 Berlin 10623 Germany
- Department of ChemistryUniversity of Manitoba 144 Dysart Rd, 360 Parker Building R3T 2 N2 Winnipeg, MB Canada
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González JA, Martínez FJ, Sanz LF, Hevia F, de la Fuente IG, Cobos JC. Volumetric and Viscosimetric Measurements for Methanol + CH3–O–(CH2CH2O)n–CH3 (n = 2, 3, 4) Mixtures at (293.15–303.15) K and Atmospheric Pressure: Application of the ERAS Model. J SOLUTION CHEM 2020. [DOI: 10.1007/s10953-020-00964-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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38
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Chernikova EY, Ruleva AY, Tsvetkov VB, Fedorov YV, Novikov VV, Aliyeu TM, Pavlov AA, Shepel NE, Fedorova OA. Cucurbit[7]uril-driven modulation of ligand-DNA interactions by ternary assembly. Org Biomol Chem 2020; 18:755-766. [PMID: 31912862 DOI: 10.1039/c9ob02543j] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The design of small organic molecules with a predictable and desirable DNA-binding mechanism is a topical research task for biomedicine application. Herein, we demonstrate an attractive supramolecular strategy for controlling the non-covalent ligand-DNA interaction by binding with cucurbituril as a synthetic receptor. With a combination of UV/vis, CD and NMR experiments, we demonstrate that the bis-styryl dye with two suitable binding sites can involve double stranded DNA and cucurbituril in the formation of the supramolecular triad. The ternary assembly is formed as a result of the interaction of macrocyclic cucurbituril with one pyridinium fragment of the bis-styryl dye, while the second pyridinium fragment of the dye is effectively associated with DNA backbones, which leads to a change in the ligand-DNA binding mode from aggregation to a minor groove. This exciting outcome was supported by molecular docking studies that help to understand the molecular orientation of the supramolecular triad and elucidate the destruction of dye aggregates caused by cucurbituril. These studies provide valuable information on the mechanisms of DNA binding to small molecules and recognition processes in bioorganic supramolecular assemblies constructed from multiple non-covalent interactions.
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Affiliation(s)
- Ekaterina Y Chernikova
- Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia.
| | - Anna Y Ruleva
- Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia.
| | - Vladimir B Tsvetkov
- Computational Oncology Group, I.M. Sechenov First Moscow State Medical University, Trubetskaya str, 8/2, Moscow, 119146 Russia and Biophysics Department, Research and Clinical Center for Physical Chemical Medicine, Malaya Pirogovskaya str. 1a, Moscow 119435, Russia and Polyelectrolytes and Biomedical Polymers Laboratory, A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky prospect str. 29, Moscow, 119991, Russia
| | - Yuri V Fedorov
- Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia.
| | - Valentin V Novikov
- Laboratory of Nuclear Magnetic Resonances, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia
| | - Tseimur M Aliyeu
- Center for Molecule Composition Studies, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia
| | - Alexander A Pavlov
- Laboratory of Nuclear Magnetic Resonances, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia
| | - Nikolay E Shepel
- Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia.
| | - Olga A Fedorova
- Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Moscow, 119991, Russia.
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39
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Hellwig H, Nowok A, Małecki JG, Kuś P, Jędrzejowska A, Grzybowska K, Pawlus S. Conformational analysis and molecular dynamics of glass-forming aromatic thiacrown ethers. Phys Chem Chem Phys 2020; 22:17948-17959. [DOI: 10.1039/d0cp02585b] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The dielectric properties, glass transition temperature and molecular dynamics of thiacrown ethers are strongly dependent on the thiacrown ring type.
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Affiliation(s)
- Hubert Hellwig
- Institute of Chemistry
- University of Silesia
- 40-006 Katowice
- Poland
| | - Andrzej Nowok
- August Chełkowski Institute of Physics
- University of Silesia
- 41-500 Chorzów
- Poland
| | | | - Piotr Kuś
- Institute of Chemistry
- University of Silesia
- 40-006 Katowice
- Poland
| | | | | | - Sebastian Pawlus
- August Chełkowski Institute of Physics
- University of Silesia
- 41-500 Chorzów
- Poland
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40
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An L, Wang C, Han L, Liu J, Huang T, Zheng Y, Yan C, Sun J. Structural Design, Synthesis, and Preliminary Biological Evaluation of Novel Dihomooxacalix[4]arene-Based Anti-tumor Agents. Front Chem 2019; 7:856. [PMID: 31921778 PMCID: PMC6923765 DOI: 10.3389/fchem.2019.00856] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 11/25/2019] [Indexed: 12/22/2022] Open
Abstract
Calixarene and its derivatives have extensively served as promising anti-tumor agents. Previously, we have synthesized a series of calix[n]arene polyhydroxyamine derivatives (n = 4, 6, 8) and found that 5,11,17,23-tetra-tert-butyl-25,27-bis [N-(2-hydroxyethyl)aminocarbonylmethoxyl] calix[4]arene (CLX-4) displayed significant effect toward SKOV3, A549, SW1990, HeLa, Raji, and MDA-MB-231 cancer cells. In the present work, we find a replacement of calix[4]arene bone and synthesized 19 novel structurally related dihomooxacalix[4]arene amide derivatives 4A-4S to optimize its efficacy. Their abilities to induce cytotoxicity in human lung carcinoma (A549) cells, breast cancer (MCF-7) cells, cervical cancer (HeLa) cells, hepatocellular carcinoma (HepG2) cells, as well as human umbilical vein endothelial (HUVEC) cells are evaluated in vitro. Encouraging results show that the majority of dihomooxacalix[4]arene amide derivatives are effective at inhibiting A549 cell proliferation with the corresponding IC50 ranging from 0.6 to 20.1 μM. In particular, compounds 4A, 4D, and 4L explore markedly increased potency (IC50 value is 2.0 ± 0.5 μM, 0.7 ± 0.1 μM, and 1.7 ± 0.4 μM) over the cytotoxicity profiles of control CLX-4, whose IC50 value is 2.8 ± 0.3 μM. More interestingly, 4A also demonstrates the perfect cytotoxic effect against MCF-7, HeLa, and HepG2 cells with IC50 values of 1.0 ± 0.1 μM, 0.8 ± 0.2 μM, and 2.7 ± 0.4 μM. In addition, the results proved that our synthesized 4A has much lower toxicity (41%) to normal cells at a concentration of 10 μM than that of 4D (90%). To reveal the mechanisms, the key indicators including the cell cycle and apoptosis are observed by the flow cytometry analysis in MCF-7 cells. The results demonstrate that both 4A and 4D can induce the MCF-7 cell cycle arrest in G0/G1 phase and cell apoptosis. Therefore, our finding proves that the dihomooxacalix[4]arene amide derivatives are convenient platforms for potential supramolecular anticancer agents.
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Affiliation(s)
- Lin An
- College of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Chan Wang
- College of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Lili Han
- Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China
| | - Jiadong Liu
- College of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Tonghui Huang
- College of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Youguang Zheng
- College of Pharmacy, Xuzhou Medical University, Xuzhou, China.,Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Chaoguo Yan
- College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China
| | - Jing Sun
- College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China
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41
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Lee D, Lee S, Noh I, Oh E, Ryu H, Ha J, Jeong S, Yoo J, Jeon T, Yun C, Kim Y. A Helical Polypeptide-Based Potassium Ionophore Induces Endoplasmic Reticulum Stress-Mediated Apoptosis by Perturbing Ion Homeostasis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2019; 6:1801995. [PMID: 31380199 PMCID: PMC6661937 DOI: 10.1002/advs.201801995] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 04/22/2019] [Indexed: 05/30/2023]
Abstract
Perturbation of potassium homeostasis can affect various cell functions and lead to the onset of programmed cell death. Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death are unclear and the bioapplicability is limited. In this study, helical polypeptide-based potassium ionophores are developed to induce endoplasmic reticulum (ER) stress-mediated apoptosis. The polypeptide-based potassium ionophores disturb ion homeostasis and then induce prolonged ER stress in the cells. The ER stress results in oxidative environments that accelerate the activation of mitochondria-dependent apoptosis. Moreover, ER stress-mediated apoptosis is triggered in a tumor-bearing mouse model that suppresses tumor proliferation. This study provides the first evidence showing that helical polypeptide-based potassium ionophores trigger ER stress-mediated apoptosis by perturbation of potassium homeostasis.
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Affiliation(s)
- DaeYong Lee
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
| | - Soo‐Hwan Lee
- Department of BioengineeringCollege of EngineeringHanyang UniversitySeoul04763Republic of Korea
| | - Ilkoo Noh
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
| | - Eonju Oh
- Department of BioengineeringCollege of EngineeringHanyang UniversitySeoul04763Republic of Korea
| | - Hyunil Ryu
- Department of Biological EngineeringInha UniversityIncheon22212Republic of Korea
| | - JongHoon Ha
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
| | - SeongDong Jeong
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
| | - Jisang Yoo
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
| | - Tae‐Joon Jeon
- Department of Biological EngineeringInha UniversityIncheon22212Republic of Korea
| | - Chae‐Ok Yun
- Department of BioengineeringCollege of EngineeringHanyang UniversitySeoul04763Republic of Korea
| | - Yeu‐Chun Kim
- Department of Chemical and Biomolecular EngineeringKorea Advanced Institute of Science and Technology (KAIST)Daejeon34141Republic of Korea
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42
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Moiseev RV, Morrison PWJ, Steele F, Khutoryanskiy VV. Penetration Enhancers in Ocular Drug Delivery. Pharmaceutics 2019; 11:E321. [PMID: 31324063 PMCID: PMC6681039 DOI: 10.3390/pharmaceutics11070321] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 07/01/2019] [Accepted: 07/03/2019] [Indexed: 12/12/2022] Open
Abstract
There are more than 100 recognized disorders of the eye. This makes the development of advanced ocular formulations an important topic in pharmaceutical science. One of the ways to improve drug delivery to the eye is the use of penetration enhancers. These are defined as compounds capable of enhancing drug permeability across ocular membranes. This review paper provides an overview of anatomical and physiological features of the eye and discusses some common ophthalmological conditions and permeability of ocular membranes. The review also presents the analysis of literature on the use of penetration-enhancing compounds (cyclodextrins, chelating agents, crown ethers, bile acids and bile salts, cell-penetrating peptides, and other amphiphilic compounds) in ocular drug delivery, describing their properties and modes of action.
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Affiliation(s)
- Roman V Moiseev
- Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box 224, Reading RG66AD, UK
| | - Peter W J Morrison
- Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box 224, Reading RG66AD, UK
| | - Fraser Steele
- MC2 Therapeutics, James House, Emlyn Lane, Leatherhead KT22 7EP, UK
| | - Vitaliy V Khutoryanskiy
- Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box 224, Reading RG66AD, UK.
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43
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Stredansky M, Turco E, Feng Z, Costantini R, Comelli G, Verdini A, Floreano L, Morgante A, Dri C, Cossaro A. On-surface trapping of alkali atoms by crown ethers in ultra high vacuum. NANOSCALE ADVANCES 2019; 1:1721-1725. [PMID: 36134236 PMCID: PMC9419578 DOI: 10.1039/c9na00144a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 04/02/2019] [Indexed: 06/16/2023]
Abstract
Crown ethers, assembled into a regular 2D array via a chemical guest-host recognition process, have been successfully employed to trap sodium atoms on a surface, under ultra-high vacuum conditions.
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Affiliation(s)
- Matus Stredansky
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Elia Turco
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Zhijing Feng
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Roberto Costantini
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Giovanni Comelli
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Alberto Verdini
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
| | - Luca Floreano
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
| | - Alberto Morgante
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Carlo Dri
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
- Dipartimento di Fisica, Università di Trieste via A. Valerio 2 I-34127 Trieste Italy
| | - Albano Cossaro
- CNR-IOM Laboratorio TASC Basovizza SS-14, km 163.5 I-34012 Trieste Italy
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44
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Adamovich SN. New atranes and similar ionic complexes. Synthesis, structure, properties. Appl Organomet Chem 2019. [DOI: 10.1002/aoc.4940] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Sergey N. Adamovich
- A. E. Favorsky Irkutsk Institute of ChemistrySB RAS 1 Favorsky Street 664033 Irkutsk Russian Federation
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45
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Affiliation(s)
- Takeshi Yokoyama
- Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0914, Japan
| | - Mineyuki Mizuguchi
- Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0914, Japan
- Graduate School of Innovative Life Science, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
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46
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Koçoğlu S, Ogutcu H, Hayvalı Z. Photophysical and antimicrobial properties of new double-armed benzo-15-crown-5 ligands and complexes. RESEARCH ON CHEMICAL INTERMEDIATES 2019. [DOI: 10.1007/s11164-019-03741-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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47
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Carreira-Barral I, Rumbo C, Mielczarek M, Alonso-Carrillo D, Herran E, Pastor M, Del Pozo A, García-Valverde M, Quesada R. Small molecule anion transporters display in vitro antimicrobial activity against clinically relevant bacterial strains. Chem Commun (Camb) 2019; 55:10080-10083. [DOI: 10.1039/c9cc04304g] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains.
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Affiliation(s)
| | - Carlos Rumbo
- Departamento de Química, Universidad de Burgos
- Burgos 09001
- Spain
- International Research Centre in Critical Raw Materials-ICCRAM
- Universidad de Burgos
| | | | | | - Enara Herran
- Biokeralty Research Institute AIE
- Hermanos Lumière 5
- 01510 Miñano
- Spain
| | - Marta Pastor
- Biokeralty Research Institute AIE
- Hermanos Lumière 5
- 01510 Miñano
- Spain
| | - Angel Del Pozo
- Biokeralty Research Institute AIE
- Hermanos Lumière 5
- 01510 Miñano
- Spain
| | | | - Roberto Quesada
- Departamento de Química, Universidad de Burgos
- Burgos 09001
- Spain
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48
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Guberović I, Marjanović M, Mioč M, Ester K, Martin-Kleiner I, Šumanovac Ramljak T, Mlinarić-Majerski K, Kralj M. Crown ethers reverse P-glycoprotein-mediated multidrug resistance in cancer cells. Sci Rep 2018; 8:14467. [PMID: 30262858 PMCID: PMC6160470 DOI: 10.1038/s41598-018-32770-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 09/12/2018] [Indexed: 01/02/2023] Open
Abstract
Multidrug resistance (MDR) is a widespread phenomenon exhibited by many cancers and represents a fundamental obstacle for successful cancer treatments. Tumour cells commonly achieve MDR phenotype through overexpression and/or increased activity of ABC transporters. P-glycoprotein transporter (P-gp, ABCB1) is a major cause of MDR and therefore represents a valuable target for MDR reversal. Several naturally occurring potassium ionophores (e.g. salinomycin) were shown to inhibit P-gp effectively. We have previously shown antitumour activity of a number of 18-crown-6 ether compounds that transport potassium ions across membranes. Here we present data on P-gp inhibitory activity of 16 adamantane-substituted monoaza- and diaza-18-crown-6 ether compounds, and their effect on MDR reversal in model cell lines. We show that crown ether activity depends on their lipophilicity as well as on the linker to adamantane moiety. The most active crown ethers were shown to be more effective in sensitising MDR cells to paclitaxel and adriamycin than verapamil, a well-known P-gp inhibitor. Altogether our data demonstrate a novel use of crown ethers for inhibition of P-gp and reversal of MDR phenotype.
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Affiliation(s)
- Iva Guberović
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia.,Josep Carreras Leukaemia Research Institute, Campus ICO-Germans Trias i Pujol-Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Marko Marjanović
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia
| | - Marija Mioč
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia
| | - Katja Ester
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia
| | - Irena Martin-Kleiner
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia
| | - Tatjana Šumanovac Ramljak
- Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia
| | - Kata Mlinarić-Majerski
- Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia
| | - Marijeta Kralj
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia.
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49
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Adamiak M, Porwański S, Ignaczak A. Conformational search and spectroscopic analysis of bis -β- d -glucopyranosyl azacrown derivative. Tetrahedron 2018. [DOI: 10.1016/j.tet.2018.03.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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50
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Sathiyajith C, Shaikh RR, Han Q, Zhang Y, Meguellati K, Yang YW. Biological and related applications of pillar[n]arenes. Chem Commun (Camb) 2018; 53:677-696. [PMID: 27942626 DOI: 10.1039/c6cc08967d] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Pillar[n]arenes are a new class of synthetic supramolecular macrocycles streamlined by their particular pillar-shaped architecture which consists of an electron-rich cavity and two fine-tuneable rims. The ease and diversity of the functionalization of the two rims open possibilities for the design of new architectures, topological isomers, and scaffolds. Significantly, this emerging class of macrocyclic receptors offers a unique platform for biological purposes. This review article covers the most recent contributions from the pillar[n]arene field in terms of artificial membrane transport systems, controlled drug delivery systems, biomedical imaging, biosensors, cell adhesion, fluorescent sensing, and pesticide detection based on host-guest interactions. The review also uniquely describes the properties of sub-units that make pillar[n]arenes suitable for biological applications and it provides a detailed outline for the design of new innovative pillar-like structures with specific properties to open up a new avenue for pillar[n]arene chemistry.
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Affiliation(s)
- CuhaWijay Sathiyajith
- International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
| | - Rafik Rajjak Shaikh
- International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
| | - Qian Han
- International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
| | - Yue Zhang
- The First Clinical College, Harbin Medical University, 23 Youzheng Street, Harbin, 150001, P. R. China.
| | - Kamel Meguellati
- International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
| | - Ying-Wei Yang
- International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, P. R. China.
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