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1
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Sabt A, Khaleel EF, Shaldam MA, Ebaid MS, Mustafa Badi R, Allayeh AK, Eldehna WM, Dziadek J. Discovery of new quinoline derivatives bearing 1-aryl-1,2,3-triazole motif as influenza H1N1 virus neuraminidase inhibitors. Bioorg Chem 2024; 151:107703. [PMID: 39137601 DOI: 10.1016/j.bioorg.2024.107703] [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: 06/11/2024] [Revised: 07/27/2024] [Accepted: 08/05/2024] [Indexed: 08/15/2024]
Abstract
Sporadically and periodically, influenza outbreaks threaten global health and the economy. Antigen drift-induced influenza virus mutations hamper antiviral drug development. Thus, a novel antiviral agent is urgently needed to address medication inefficacy issues. Herein, sixteen new quinoline-triazole hybrids 6a-h and 9a-h were prepared and evaluated in vitro against the H1N1 virus. In particular, 6d, 6e, and 9b showed promising H1N1 antiviral activity with selective index (SI) CC50/IC50 values of 15.8, 37, and 29.15. After that, the inhibition rates for various mechanisms of action (virus replication, adsorption, and virucidal activity) were investigated for the most efficient candidates 6d, 6e, and 9b. Additionally, their ability to inhibit neuraminidase was evaluated. With an IC50 value of 0.30 µM, hybrid 6d demonstrated effective and comparable inhibitory activity to Oseltamivir. Ultimately, molecular modeling investigations, encompassing molecular docking and molecular dynamic simulations, were conducted to provide a scientific basis for the observed antiviral results.
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Affiliation(s)
- Ahmed Sabt
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Center, Dokki, Cairo 12622, Egypt.
| | - Eman F Khaleel
- Department of Medical Physiology, College of Medicine, King Khalid University, Asir 61421, Saudi Arabia
| | - Moataz A Shaldam
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
| | - Manal S Ebaid
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Center, Dokki, Cairo 12622, Egypt; Department of Chemistry, College of Science, Northern Border University, Arar, Saudi Arabia
| | - Rehab Mustafa Badi
- Department of Medical Physiology, College of Medicine, King Khalid University, Asir 61421, Saudi Arabia
| | - Abdou K Allayeh
- Water Pollution Research Department, Environment and Climate Change Institute, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Wagdy M Eldehna
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt.
| | - Jaroslaw Dziadek
- Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology of the Polish Academy of Sciences, Lodz, Poland
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2
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Hegedűs D, Szemerédi N, Petrinca K, Berkecz R, Spengler G, Szatmári I. Synthesis of Tumor Selective Indole and 8-Hydroxyquinoline Skeleton Containing Di-, or Triarylmethanes with Improved Cytotoxic Activity. Molecules 2024; 29:4176. [PMID: 39275023 PMCID: PMC11396803 DOI: 10.3390/molecules29174176] [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: 08/06/2024] [Revised: 08/26/2024] [Accepted: 08/30/2024] [Indexed: 09/16/2024] Open
Abstract
The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported. The formed Mannich base 10 was subjected to give bioconjugates with indole and 7-azaindole. The effect of the aldehyde component and the amine part of the Mannich base on the synthetic pathway was also investigated. In favor of having a preliminary overview of the structure-activity relationships, the derivatives have been tested on cancer and normal cell lines. In the case of bioconjugate 16, as the most powerful scaffold in the series bearing indole and a 5-chloro-8-hydroxyquinoline skeleton, a potent toxic activity against the resistant Colo320 colon adenocarcinoma cell line was observed. Furthermore, this derivative was selective towards cancer cell lines showing no toxicity on non-tumor fibroblast cells.
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Affiliation(s)
- Dóra Hegedűs
- Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - Nikoletta Szemerédi
- Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary (G.S.)
| | - Krisztina Petrinca
- Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - Róbert Berkecz
- Institute of Pharmaceutical Analysis, University of Szeged, Somogyi u. 4, H-6720 Szeged, Hungary;
- Department of Forensic Medicine, Albert Szent-Györgyi Health Center, Kossuth Lajos sgt. 40, H-6724 Szeged, Hungary
| | - Gabriella Spengler
- Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary (G.S.)
| | - István Szatmári
- Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
- HUN-REN–SZTE Stereochemistry Research Group, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
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3
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Zieba A, Pindjakova D, Latocha M, Plonka-Czerw J, Kusmierz D, Cizek A, Jampilek J. Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides. Molecules 2024; 29:4044. [PMID: 39274892 PMCID: PMC11396667 DOI: 10.3390/molecules29174044] [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: 06/26/2024] [Revised: 08/21/2024] [Accepted: 08/24/2024] [Indexed: 09/16/2024] Open
Abstract
A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a-f and 6a-f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a-h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a-d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a-f and 6a-f and 1,2,3-triazole derivatives 7a-h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a-f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.
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Affiliation(s)
- Andrzej Zieba
- Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellonska 4, 41-200 Sosnowiec, Poland
| | - Dominika Pindjakova
- Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic
| | - Malgorzata Latocha
- Department of Cell Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 9, 41-200 Sosnowiec, Poland
| | - Justyna Plonka-Czerw
- Department of Cell Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 9, 41-200 Sosnowiec, Poland
| | - Dariusz Kusmierz
- Department of Cell Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jednosci 9, 41-200 Sosnowiec, Poland
| | - Alois Cizek
- Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic
| | - Josef Jampilek
- Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland
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4
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Pindjakova D, Mascaretti S, Hricoviniova J, Hosek J, Gregorova J, Kos J, Cizek A, Hricoviniova Z, Jampilek J. Critical view on antimicrobial, antibiofilm and cytotoxic activities of quinazolin-4(3 H)-one derived schiff bases and their Cu(II) complexes. Heliyon 2024; 10:e29051. [PMID: 38601653 PMCID: PMC11004567 DOI: 10.1016/j.heliyon.2024.e29051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 04/12/2024] Open
Abstract
A series of nine 2,3-disubstituted-quinazolin-4(3H)-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084. While anti-enterococcal and antimycobacterial activities were insignificant, 3-[(E)-(2-hydroxy-5-nitrobenzylidene)amino]-2-(2-hydroxy-5-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (SB3) and its Cu(II) complex (SB3-Cu) demonstrated bacteriostatic antistaphylococcal activity. In addition, both compounds, as well as the other two prepared complexes, showed antibiofilm activity, which resulted in a reduction of biofilm formation and eradication of mature S. aureus biofilm by 80% even at concentrations lower than the values of their minimum inhibitory concentrations. In addition, the compounds were tested for their cytotoxic effect on the human monocytic leukemia cell line THP-1. The antileukemic efficiency was improved by the preparation of Cu(II) complexes from the corresponding non-chelated Schiff base ligands.
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Affiliation(s)
- Dominika Pindjakova
- Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia
| | - Sarka Mascaretti
- Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic
| | - Jana Hricoviniova
- Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia
| | - Jan Hosek
- Department of Pharmacology and Toxicology, Veterinary Research Institute, Hudcova 296/70, 621 00 Brno, Czech Republic
| | - Jana Gregorova
- Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Jiri Kos
- Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia
- Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Alois Cizek
- Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic
| | - Zuzana Hricoviniova
- Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia
| | - Josef Jampilek
- Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia
- Department of Chemical Biology, Faculty of Science, Palacky University Olomouc, Slechtitelu 27, 783 71 Olomouc, Czech Republic
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5
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Memedovski R, Preza M, Müller J, Kämpfer T, Rufener R, de Souza MVN, da Silva ET, de Andrade GF, Braga S, Uldry AC, Buchs N, Heller M, Lundström-Stadelmann B. Investigation of the mechanism of action of mefloquine and derivatives against the parasite Echinococcus multilocularis. Int J Parasitol Drugs Drug Resist 2023; 21:114-124. [PMID: 36921443 PMCID: PMC10025029 DOI: 10.1016/j.ijpddr.2023.03.002] [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: 12/14/2022] [Revised: 03/03/2023] [Accepted: 03/05/2023] [Indexed: 03/12/2023]
Abstract
Alveolar echinococcosis (AE) is caused by infection with the fox tapeworm E. multilocularis. The disease affects humans, dogs, captive monkeys, and other mammals, and it is caused by the metacestode stage of the parasite growing invasively in the liver. The current drug treatment is based on non-parasiticidal benzimidazoles. Thus, they are only limitedly curative and can cause severe side effects. Therefore, novel and improved treatment options for AE are needed. Mefloquine (MEF), an antimalarial agent, was previously shown to be effective against E. multilocularis in vitro and in experimentally infected mice. However, MEF is not parasiticidal and needs improvement for successful treatment of patients, and it can induce strong neuropsychiatric side-effects. In this study, the structure-activity relationship and mode of action of MEF was investigated by comparative analysis of 14 MEF derivatives. None of them showed higher activity against E. multilocularis metacestodes compared to MEF, but four compounds caused limited damage. In order to identify molecular targets of MEF and effective derivatives, differential affinity chromatography combined with mass spectrometry was performed with two effective compounds (MEF, MEF-3) and two ineffective compounds (MEF-13, MEF-22). 1'681 proteins were identified that bound specifically to MEF or derivatives. 216 proteins were identified as binding only to MEF and MEF-3. GO term enrichment analysis of these proteins and functional grouping of the 25 most abundant MEF and MEF-3 specific binding proteins revealed the key processes energy metabolism and cellular transport and structure, as well as stress responses and nucleic acid binding to be involved. The previously described ferritin was confirmed as an exclusively MEF-binding protein that could be relevant for its efficacy against E. multilocularis. The here identified potential targets of MEF will be further investigated in the future for a clear understanding of the pleiotropic effects of MEF, and improved therapeutic options against AE.
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Affiliation(s)
- Roman Memedovski
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Matías Preza
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Joachim Müller
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Tobias Kämpfer
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Reto Rufener
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | | | - Emerson Teixeira da Silva
- Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos - Far Manguinhos, 21041-250, Rio de Janeiro, Brazil
| | | | - Sophie Braga
- Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Anne-Christine Uldry
- Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Natasha Buchs
- Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Manfred Heller
- Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Britta Lundström-Stadelmann
- Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.
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6
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Amin MM, Abuo-Rahma GEDA, Shaykoon MSA, Marzouk AA, Abourehab MAS, Saraya RE, Badr M, Sayed AM, Beshr EAM. Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition. Bioorg Chem 2023; 134:106444. [PMID: 36893547 DOI: 10.1016/j.bioorg.2023.106444] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 02/18/2023] [Accepted: 02/21/2023] [Indexed: 02/26/2023]
Abstract
The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC50 = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC50 = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC50 = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC50 = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/β-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and β-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition.
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Affiliation(s)
- Mohammed M Amin
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | - Gamal El-Din A Abuo-Rahma
- Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61519, Egypt.
| | - Montaser Sh A Shaykoon
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | - Adel A Marzouk
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS 38677, USA
| | - Mohammed A S Abourehab
- Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Roshdy E Saraya
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42515, Egypt
| | - Mohamed Badr
- Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt
| | - Ahmed M Sayed
- Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, Egypt
| | - Eman A M Beshr
- Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
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7
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Cheng H, Fu L, Yang X, Yang Y, Zhang Z, Tao Y, Wan J, Tu Z, Chen J, Li Y. Screening and identification of 3-aryl-quinolin-2-one derivatives as antiviral agents against influenza A. J Med Virol 2023; 95:e28327. [PMID: 36415105 DOI: 10.1002/jmv.28327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 11/03/2022] [Accepted: 11/20/2022] [Indexed: 11/24/2022]
Abstract
Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 μM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.
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Affiliation(s)
- Huimin Cheng
- XtalPi Inc. (Shenzhen Jingtai Technology Co., Ltd), Shenzhen, China
| | - Liangbing Fu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
| | - Xia Yang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Yujian Yang
- Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China
| | - Zhening Zhang
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Yuan Tao
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
| | - Junting Wan
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Zhengchao Tu
- International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, China
| | - Jianxin Chen
- Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Yingjun Li
- Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China.,State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, China
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8
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Pivarcsik T, Pósa V, Kovács H, May NV, Spengler G, Pósa SP, Tóth S, Nezafat Yazdi Z, Özvegy-Laczka C, Ugrai I, Szatmári I, Szakács G, Enyedy ÉA. Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells. Int J Mol Sci 2022; 24:ijms24010593. [PMID: 36614037 PMCID: PMC9820345 DOI: 10.3390/ijms24010593] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 12/31/2022] Open
Abstract
Multidrug resistance (MDR) in cancer is one of the major obstacles of chemotherapy. We have recently identified a series of 8-hydroxyquinoline Mannich base derivatives with MDR-selective toxicity, however with limited solubility. In this work, a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(η5-C5Me5) and Ru(η6-p-cymene) complexes with excellent aqueous solubility were developed, characterized, and tested against sensitive and MDR cells. Complex formation of the ligand with essential metal ions was also investigated using UV-visible, circular dichroism, 1H NMR (Zn(II)), and electron paramagnetic resonance (Cu(II)) spectroscopic methods. Formation of mono and bis complexes was found in all cases with versatile coordination modes, while tris complexes were also formed with Fe(II) and Fe(III) ions, revealing the metal binding affinity of the ligand at pH 7.4: Cu(II) > Zn(II) > Fe(II) > Fe(III). The ligand and its Rh(III) complex displayed enhanced cytotoxicity against the resistant MES-SA/Dx5 and Colo320 human cancer cell lines compared to their chemosensitive counterparts. Both organometallic complexes possess high stability in solution, however the Ru(II) complex has lower chloride ion affinity and slower ligand exchange processes, along with the readiness to lose the arene ring that is likely connected to its inactivity.
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Affiliation(s)
- Tamás Pivarcsik
- MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
| | - Vivien Pósa
- MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
| | - Hilda Kovács
- MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
| | - Nóra V. May
- Centre for Structural Science, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
| | - Gabriella Spengler
- MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Department of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary
| | - Szonja P. Pósa
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
- National Laboratory for Drug Research and Development, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
| | - Szilárd Tóth
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
- National Laboratory for Drug Research and Development, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
| | - Zeinab Nezafat Yazdi
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
| | - Csilla Özvegy-Laczka
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
| | - Imre Ugrai
- Institute of Pharmaceutical Chemistry and Stereochemistry Research Group, Eötvös Loránd Research Network, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - István Szatmári
- Institute of Pharmaceutical Chemistry and Stereochemistry Research Group, Eötvös Loránd Research Network, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - Gergely Szakács
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, H-1117 Budapest, Hungary
- Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria
| | - Éva A. Enyedy
- MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
- Correspondence:
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9
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DPPH and Nitric Oxide Free Radical Scavenging Potential of Phenyl Quinoline Derivatives and Their Transition Metal Complexes. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.134058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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10
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Ogbu IM, Kurtay G, Robert F, Landais Y. Oxamic acids: useful precursors of carbamoyl radicals. Chem Commun (Camb) 2022; 58:7593-7607. [PMID: 35735051 DOI: 10.1039/d2cc01953a] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This review article describes the recent development in the chemistry of carbamoyl radicals generated from oxamic acids. This mild and efficient method compares well with previous methods of generation of these nucleophilic radicals. The oxidative decarboxylation of oxamic acids can be mediated through thermal, photochemical, electrochemical or photoelectrochemical means, generating carbamoyl radicals, which may further add to unsaturated systems to provide a broad range of important amides. Oxidative decarboxylation of oxamic acids also offers a straightforward entry for the preparation of urethanes, ureas, and thioureas.
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Affiliation(s)
- Ikechukwu Martin Ogbu
- University of Bordeaux, Institute of Molecular Sciences (ISM), UMR-CNRS 5255, 351, Cours de la Libération, 33405 Talence, Cedex, France. .,Alex Ekwueme Federal University, Department of Chemistry, Faculty of Sciences, Ndufu-Alike Ikwo, Abakaliki, Ebonyi State, Nigeria
| | - Gülbin Kurtay
- University of Bordeaux, Institute of Molecular Sciences (ISM), UMR-CNRS 5255, 351, Cours de la Libération, 33405 Talence, Cedex, France. .,University of Ankara, Department of Chemistry, Faculty of Science, Ankara, Turkey
| | - Frédéric Robert
- University of Bordeaux, Institute of Molecular Sciences (ISM), UMR-CNRS 5255, 351, Cours de la Libération, 33405 Talence, Cedex, France.
| | - Yannick Landais
- University of Bordeaux, Institute of Molecular Sciences (ISM), UMR-CNRS 5255, 351, Cours de la Libération, 33405 Talence, Cedex, France.
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11
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Kumar A, Dhameliya TM, Sharma K, Patel KA, Hirani RV. Environmentally Benign Approaches towards the Synthesis of Quinolines. ChemistrySelect 2022. [DOI: 10.1002/slct.202201059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Asim Kumar
- Amity Institute of Pharmacy Amity University Haryana, Panchgaon, Manesar 122 413 Haryana India
| | - Tejas M. Dhameliya
- Department of Pharmaceutical Chemistry and Quality Assurance L. M. College of Pharmacy, Navrangpura, Ahmedabad 380 009 Gujarat India
| | - Kirti Sharma
- Amity Institute of Pharmacy Amity University Haryana, Panchgaon, Manesar 122 413 Haryana India
| | - Krupa A. Patel
- Department of Pharmaceutical Chemistry and Quality Assurance L. M. College of Pharmacy, Navrangpura, Ahmedabad 380 009 Gujarat India
| | - Rajvi V. Hirani
- Department of Pharmaceutical Chemistry and Quality Assurance L. M. College of Pharmacy, Navrangpura, Ahmedabad 380 009 Gujarat India
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12
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Spasova M, Manolova N, Rashkov I, Naydenov M. Eco-Friendly Hybrid PLLA/Chitosan/ Trichoderma asperellum Nanomaterials as Biocontrol Dressings against Esca Disease in Grapevines. Polymers (Basel) 2022; 14:polym14122356. [PMID: 35745931 PMCID: PMC9228446 DOI: 10.3390/polym14122356] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/30/2022] [Accepted: 06/06/2022] [Indexed: 02/01/2023] Open
Abstract
Fungi constitute the largest number of plant pathogens and are responsible for a range of serious plant diseases. Phaeomoniella chlamydospora (P. chlamydospora) and Phaeoacremonium aleophilum (P. aleophilum) are the main fungal pathogens causing esca disease in grapevines. On the other hand, there are beneficial microorganisms such as Trichoderma spp., which are able to control the growth of many phytopathogens. In the present study, innovative, eco-friendly hybrid nanomaterials were created by electrospinning PLLA, followed by the formation of a film of chitosan/Trichoderma asperellum (T. asperellum) spores on the fibers. The polymer carrier used in this study plays an active role in ensuring the viability of the biological agent during storage and, when placed in contact with moisture, ensures the agent’s normal development. Oligochitosan, as well as low molecular weight and high molecular weight chitosan, were used. The effects of chitosan molecular weight on the dynamic viscosity of chitosan solutions, film formation, mechanical properties, spore incorporation and growth were studied. The morphology of the prepared nanomaterials, and the presence of a film based on the formation of chitosan/T. asperellum spores on the PLLA fibers, were examined using scanning electron microscopy (SEM). The surface chemical compositions of the fibrous materials were studied using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The mechanical properties of the obtained materials were also tested. The microbiological screening that was performed revealed that the eco-friendly hybrid nanomaterials incorporated with the beneficial microorganism, T. asperellum, to hamper the growth of the pathogenic P. chlamydospora and P. aleophilum fungi. The suppression rate depended on the viscosity of the chitosan solution used for the film formation. The use of oligochitosan resulted in the most effective infection of the material with T. asperellum spores. The environmentally friendly hybrid nanomaterials obtained in this study—in which the bioagent was embedded—are promising bioactive dressings for protecting grapevines against esca disease.
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Affiliation(s)
- Mariya Spasova
- Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, bl. 103A, BG-1113 Sofia, Bulgaria; (N.M.); (I.R.)
- Correspondence:
| | - Nevena Manolova
- Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, bl. 103A, BG-1113 Sofia, Bulgaria; (N.M.); (I.R.)
| | - Iliya Rashkov
- Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, bl. 103A, BG-1113 Sofia, Bulgaria; (N.M.); (I.R.)
| | - Mladen Naydenov
- Department of Microbiology, Agricultural University, BG-4000 Plovdiv, Bulgaria;
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13
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Pape VFS, Palkó R, Tóth S, Szabó MJ, Sessler J, Dormán G, Enyedy ÉA, Soós T, Szatmári I, Szakács G. Structure-Activity Relationships of 8-Hydroxyquinoline-Derived Mannich Bases with Tertiary Amines Targeting Multidrug-Resistant Cancer. J Med Chem 2022; 65:7729-7745. [PMID: 35613553 PMCID: PMC9189845 DOI: 10.1021/acs.jmedchem.2c00076] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
![]()
A recently proposed
strategy to overcome multidrug resistance (MDR)
in cancer is to target the collateral sensitivity of otherwise resistant
cells. We designed a library of 120 compounds to explore the chemical
space around previously identified 8-hydroxyquinoline-derived Mannich
bases with robust MDR-selective toxicity. We included compounds to
study the effect of halogen and alkoxymethyl substitutions in R5 in
combination with different Mannich bases in R7, a shift of the Mannich
base from R7 to R5, as well as the introduction of an aromatic moiety.
Cytotoxicity tests performed on a panel of parental and MDR cells
highlight a strong influence of experimentally determined pKa values of the donor atom moieties, indicating
that protonation and metal chelation are important factors modulating
the MDR-selective anticancer activity of the studied compounds. Our
results identify structural requirements increasing MDR-selective
anticancer activity, providing guidelines for the development of more
effective anticancer chelators targeting MDR cancer.
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Affiliation(s)
- Veronika F S Pape
- Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary.,Department of Physiology, Semmelweis University, Faculty of Medicine, Tűzoltó utca 37-47, H-1094 Budapest, Hungary
| | - Roberta Palkó
- Institute of Organic Chemistry, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary
| | - Szilárd Tóth
- Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary
| | | | - Judit Sessler
- Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary
| | - György Dormán
- TargetEx Ltd., Madách Imre u 31/2., H-2120 Dunakeszi, Hungary
| | - Éva A Enyedy
- Department of Inorganic and Analytical Chemistry, MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
| | - Tibor Soós
- Institute of Organic Chemistry, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary
| | - István Szatmári
- Institute of Pharmaceutical Chemistry and Stereochemistry Research Group of Hungarian Academy of Sciences, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
| | - Gergely Szakács
- Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary.,Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria
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14
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Khasawneh MA, AlKaabi A, Samadi A, Antony P, Vijayan R, Ahmed Al-Keridis L, Saadeh HA, Abutaha N. Synthesis and Biological Applications of Some Novel 8-Hydroxyquinoline Urea and Thiourea Derivatives. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.103905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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15
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Tsang NY, Li WF, Varhegyi E, Rong L, Zhang HJ. Ebola Entry Inhibitors Discovered from Maesa perlarius. Int J Mol Sci 2022; 23:ijms23052620. [PMID: 35269770 PMCID: PMC8910447 DOI: 10.3390/ijms23052620] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 11/21/2022] Open
Abstract
Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((−)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.
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Affiliation(s)
- Nga Yi Tsang
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (N.Y.T.); (W.-F.L.)
| | - Wan-Fei Li
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (N.Y.T.); (W.-F.L.)
| | - Elizabeth Varhegyi
- Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, 909 South Wolcott Ave, Chicago, IL 60612, USA;
| | - Lijun Rong
- Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, 909 South Wolcott Ave, Chicago, IL 60612, USA;
- Correspondence: (L.R.); (H.-J.Z.); Tel.: +1-312-3550203 (L.R.); +852-34112956 (H.-J.Z.)
| | - Hong-Jie Zhang
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong, China; (N.Y.T.); (W.-F.L.)
- Correspondence: (L.R.); (H.-J.Z.); Tel.: +1-312-3550203 (L.R.); +852-34112956 (H.-J.Z.)
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16
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Tabassum R, Ashfaq M, Oku H. Current Pharmaceutical Aspects of Synthetic Quinoline Derivatives. Mini Rev Med Chem 2021; 21:1152-1172. [PMID: 33319670 DOI: 10.2174/1389557520999201214234735] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 10/06/2020] [Accepted: 10/08/2020] [Indexed: 11/22/2022]
Abstract
Quinoline derivatives are considered broad-spectrum pharmacological compounds that exhibit a wide range of biological activities. Integration of quinoline moiety can improve its physical and chemical properties and also pharmacological behavior. Due to its wide range of pharmaceutical applications, it is a very popular compound to design new drugs for the treatment of multiple diseases like cancer, dengue fever, malaria, tuberculosis, fungal infections, AIDS, Alzheimer's disease and diabetes. In this review, our major focus is to pay attention to the biological activities of quinoline compounds in the treatment of these diseases such as anti-viral, anti-cancer, anti-malarial, antibacterial, anti-fungal, anti-tubercular and anti-diabetic.
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Affiliation(s)
- Rukhsana Tabassum
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Muhammad Ashfaq
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Hiroyuki Oku
- Division of Molecular Science, Graduate School of Science & Engineering Gunma University, Gunma 376-8515, Japan
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17
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Pallaval VB, Kanithi M, Meenakshisundaram S, Jagadeesh A, Alavala M, Pillaiyar T, Manickam M, Chidipi B. Chloroquine Analogs: An Overview of Natural and Synthetic Quinolines as Broad Spectrum Antiviral Agents. Curr Pharm Des 2021; 27:1185-1193. [PMID: 33308117 DOI: 10.2174/1381612826666201211121721] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/14/2020] [Indexed: 11/22/2022]
Abstract
SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, chloroquine and hydroxychloroquine, against SARS-CoV-2, have shown to be a potential area of interest for drug development due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discussed analogs of the drugs to understand the quinoline scaffold's potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways, primarily through the modification of its substituents. We studied these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle, pre and post entry. In this study, we reviewed chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of viruses. Furthermore, we reviewed the compound's potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to chloroquine can act as antivirals or attenuate symptoms through the stimulation of the host immune system or reduction of oxidative stress. Furthermore, we discuss perspectives of the drug's repurposing due to its ability to inhibit the beta-hematin formation and to be a Zinc Ionophore.
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Affiliation(s)
- Veera B Pallaval
- Department of Biotechnology, Krishna University, Machilipatnam-521003, Andhra Pradesh, India
| | - Manasa Kanithi
- Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, United States
| | | | - Achanta Jagadeesh
- Department of Pharmacy, Seoul National University, 101 Daehak-ro, Jongro-gu, Seoul 110-744, South Korea
| | - Mattareddy Alavala
- School of Life and Health Sciences, Adikavi Nannaya University, Rajahmundry, Andhra Pradesh 533296, India
| | - Thanigaimalai Pillaiyar
- Pharma Center Bonn, Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany
| | - Manoj Manickam
- Department of Chemistry, PSG Institute of Technology and Applied Research, Coimbatore, Tamil Nadu, India
| | - Bojjibabu Chidipi
- Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, United States
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18
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Tabassum R, Ashfaq M, Oku H. Development of an efficient, one-pot, multicomponent protocol for synthesis of 8-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives. J Heterocycl Chem 2021; 58:534-547. [PMID: 33362294 PMCID: PMC7753469 DOI: 10.1002/jhet.4193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/09/2020] [Accepted: 11/18/2020] [Indexed: 11/11/2022]
Abstract
A one-pot quick and efficient multicomponent reaction has been developed for the synthesis of a new series of functionalized 8-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives using 30 mol% ammonium acetate in ethanol as solvent. This economical protocol run smoothly to give variety of quinoline derivatives in 55% to 98% yield from inexpensive reagents and catalyst in mild reaction conditions. Various spectroscopic techniques like FTIR, 1H NMR and 13C NMR, MALDI-TOF-MS, and EI-MS were used to study and confirm their structure.
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Affiliation(s)
- Rukhsana Tabassum
- Department of ChemistryThe Islamia University of BahawalpurBahawalpurPakistan
| | - Muhammad Ashfaq
- Department of ChemistryThe Islamia University of BahawalpurBahawalpurPakistan
| | - Hiroyuki Oku
- Division of Molecular ScienceGraduate School of Science & Engineering, Gunma UniversityGunmaJapan
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19
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Gupta R, Luxami V, Paul K. Insights of 8-hydroxyquinolines: A novel target in medicinal chemistry. Bioorg Chem 2021; 108:104633. [PMID: 33513476 DOI: 10.1016/j.bioorg.2021.104633] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 12/15/2020] [Accepted: 01/04/2021] [Indexed: 12/20/2022]
Abstract
8-Hydroxyquinoline (8-HQ) is a significant heterocyclic scaffold in organic and analytical chemistry because of the properties of chromophore and is used to detect various metal ions and anions. But from the last 2 decades, this moiety has been drawn great attention of medicinal chemists due to its significant biological activities. Synthetic modification of 8-hydroxyquinoline is under exploration on large scale to develop more potent target-based broad spectrum drug molecules for the treatment of several life-threatening diseases such as anti-cancer, HIV, neurodegenerative disorders, etc. Metal chelation properties of 8-hydroxyquinoline and its derivatives also make these potent drug candidates for the treatment of various diseases. This review comprises 8-hydroxyquinoline derivatives reported in the literature in last five years (2016-2020) and we anticipate that it will assist medicinal chemists in the synthesis of novel and pharmacologically potent agents for various therapeutic targets, mainly anti-proliferative, anti-microbial, anti-fungal and anti-viral as well as for the treatment of neurodegenerative disorders.
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Affiliation(s)
- Rohini Gupta
- School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147 004, India
| | - Vijay Luxami
- School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147 004, India
| | - Kamaldeep Paul
- School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147 004, India.
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20
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Tabassum R, Ashfaq M, Oku H. Recent Advances in Transition Metal Free Synthetic Protocols for Quinoline Derivatives. CURR ORG CHEM 2020. [DOI: 10.2174/1385272824999200616122557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The quinoline moiety is a privileged scaffold among heterocyclic compounds
that is an important construction motif in the fields of pharmaceutical chemistry. Quinoline
molecule possesses a variety of therapeutic activities like antiviral, antimalarial, antibacterial,
antitumor, anticancer, antioxidant antihypertensive, antifungal, anthelmintic, cardiotonic,
anticonvulsant and anti-inflammatory. This review provides an insight into recent
development in transition metal free novel and modified conventional synthetic routes to
yield a wide variety of substituted quinolines.
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Affiliation(s)
- Rukhsana Tabassum
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Muhammad Ashfaq
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Hiroyuki Oku
- Division of Molecular Science, Graduate School of Science & Engineering Gunma University, Gunma 376-8515, Japan
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21
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Tabassum R, Ashfaq M, Oku H. 7-Hydroxy-4-phenyl-1, 2-dihydroquinoline derivatives: synthesis via one-pot, three-component reaction and structure elucidation. Heliyon 2020; 6:e05035. [PMID: 33020745 PMCID: PMC7527354 DOI: 10.1016/j.heliyon.2020.e05035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/23/2020] [Accepted: 09/18/2020] [Indexed: 12/27/2022] Open
Abstract
We have developed a new and facile one pot three component protocol catalyzed by ammonium acetate for construction of new functionalized 7-hydroxy-4-phenyl-1,2-dihydroquinoline derivatives. A variety of quinoline derivatives were obtained in good to excellent yield from inexpensive reagents and catalyst in mild reaction conditions that provide atom economy and cost efficacy. Various spectroscopic techniques like FTIR, 1HNMR and 13CNMR were employed to study their structure while mass of the synthesized compounds were confirmed through MALDI-TOF-MS and EI mass spectrometry.
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Affiliation(s)
- Rukhsana Tabassum
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Muhammad Ashfaq
- Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, 36100, Pakistan
| | - Hiroyuki Oku
- Division of Molecular Science, Graduate School of Science &Engineering Gunma University, Gunma, 376-8515, Japan
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22
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Saadeh HA, Sweidan KA, Mubarak MS. Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines. Molecules 2020; 25:molecules25184321. [PMID: 32967141 PMCID: PMC7571046 DOI: 10.3390/molecules25184321] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022] Open
Abstract
Compounds containing the 8-hydroxyquinoline (8-HQ) 1 nucleus exhibit a wide range of biological activities, including antimicrobial, anticancer, and antifungal effects. The chemistry and biology of this group have attracted the attention of chemists, medicinal chemists, and professionals in health sciences. A number of prescribed drugs incorporate this group, and numerous 8-HQ- based molecules can be used to develop potent lead compounds with good efficacy and low toxicity. This review focusses on the recent advances in the synthesis of 8-HQ derivatives with different pharmacological properties, including anticancer, antiviral, and antibacterial activities. For this purpose, recent relevant references were searched in different known databases and search engines, such as MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, Scientific Information Database (SID), SciFinder, and Institute for Scientific Information (ISI) Web of Knowledge. This review article provides a literature overview of the various synthetic strategies and biological activities of 8-HQ derivatives and covers the recent related literature. Taken together, compounds containing the 8-HQ moiety have huge therapeutic value and can act as potential building blocks for various pharmacologically active scaffolds. In addition, several described compounds in this review could act leads for the development of drugs against numerous diseases including cancer.
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Affiliation(s)
- Haythem A. Saadeh
- Department of Chemistry, College of Science, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates;
- Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan;
| | - Kamal A. Sweidan
- Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan;
| | - Mohammad S. Mubarak
- Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan;
- Correspondence: ; Tel.: +962-791-016-126
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Yuan JW, Chen Q, Li C, Zhu JL, Yang LR, Zhang SR, Mao P, Xiao YM, Qu LB. Silver-catalyzed direct C-H oxidative carbamoylation of quinolines with oxamic acids. Org Biomol Chem 2020; 18:2747-2757. [PMID: 32227021 DOI: 10.1039/d0ob00358a] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A silver-catalyzed efficient and direct C-H carbamoylation of quinolines with oxamic acids to access carbamoylated quinolines has been developed through oxidative decarboxylation reaction. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance and excellent yields under mild conditions.
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Affiliation(s)
- Jin-Wei Yuan
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Qian Chen
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Chuang Li
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Jun-Liang Zhu
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Liang-Ru Yang
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Shou-Ren Zhang
- Henan Key Laboratory of Nanocomposites and Applications; Institute of Nanostructured Functional Materials, Huanghe Science and Technology College, Zhengzhou 450006, China
| | - Pu Mao
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Yong-Mei Xiao
- School of Chemistry & Chemical Engineering, Henan University of Technology; Academician Workstation for Natural Medicinal Chemistry of Henan Province, Zhengzhou 450001, China.
| | - Ling-Bo Qu
- College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
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Rai M, Jamil B. Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals. Nanotheranostics 2019. [PMCID: PMC7121811 DOI: 10.1007/978-3-030-29768-8_7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Various viruses can be considered as one of the most frequent causes of human diseases, from mild illnesses to really serious sicknesses that end fatally. Numerous viruses are also pathogenic to animals and plants, and many of them, mutating, become pathogenic also to humans. Several cases of affecting humans by originally animal viruses have been confirmed. Viral infections cause significant morbidity and mortality in humans, the increase of which is caused by general immunosuppression of the world population, changes in climate, and overall globalization. In spite of the fact that the pharmaceutical industry pays great attention to human viral infections, many of clinically used antivirals demonstrate also increased toxicity against human cells, limited bioavailability, and thus, not entirely suitable therapeutic profile. In addition, due to resistance, a combination of antivirals is needed for life-threatening infections. Thus, the development of new antiviral agents is of great importance for the control of virus spread. On the other hand, the discovery and development of structurally new antivirals represent risks. Therefore, another strategy is being developed, namely the reformulation of existing antivirals into nanoformulations and investigation of various metal and metalloid nanoparticles with respect to their diagnostic, prophylactic, and therapeutic antiviral applications. This chapter is focused on nanoscale materials/formulations with the potential to be used for the treatment or inhibition of the spread of viral diseases caused by human immunodeficiency virus, influenza A viruses (subtypes H3N2 and H1N1), avian influenza and swine influenza viruses, respiratory syncytial virus, herpes simplex virus, hepatitis B and C viruses, Ebola and Marburg viruses, Newcastle disease virus, dengue and Zika viruses, and pseudorabies virus. Effective antiviral long-lasting and target-selective nanoformulations developed for oral, intravenous, intramuscular, intranasal, intrarectal, intravaginal, and intradermal applications are discussed. Benefits of nanoparticle-based vaccination formulations with the potential to secure cross protection against divergent viruses are outlined as well.
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Affiliation(s)
- Mahendra Rai
- Department of Biotechnology, Nanobiotechnology Laboratory, Amravati, Maharashtra, India, Department of Chemistry, Federal University of Piauí, Teresina, Piauí Brazil
| | - Bushra Jamil
- Department of DMLS, University of Lahore, Islamabad, Pakistan
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