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Gohari S, Reshadmanesh T, Khodabandehloo H, Karbalaee-Hasani A, Ahangar H, Arsang-Jang S, Ismail-Beigi F, Dadashi M, Ghanbari S, Taheri H, Fathi M, Muhammadi MJ, Mahmoodian R, Asgari A, Tayaranian M, Moharrami M, Mahjani M, Ghobadian B, Chiti H, Gohari S. The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial. Diabetol Metab Syndr 2022; 14:170. [PMID: 36397128 PMCID: PMC9669535 DOI: 10.1186/s13098-022-00951-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 11/11/2022] [Indexed: 11/18/2022] Open
Abstract
Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): - 1.06 pg/mL, 95% CI - 1.80; - 0.32, P = 0.006), interleukin 1β (IL-1β) and high-sensitive C-reactive protein (Hs-CRP) (adiff: - 4.58 pg/mL and - 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: - 342.51, 95% CI - 474.23; - 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: - 8.81, 95% CI - 14.87; - 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA1c, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.
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Affiliation(s)
- Sepehr Gohari
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Family Medicine, Alborz University of Medical Science, Karaj, Alborz, Iran
| | - Tara Reshadmanesh
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hadi Khodabandehloo
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amir Karbalaee-Hasani
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hassan Ahangar
- Department of Cardiology, School of Medicine, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Shahram Arsang-Jang
- Department of Biostatistics, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Faramarz Ismail-Beigi
- Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Mohsen Dadashi
- Department of Cardiology, School of Medicine, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Samin Ghanbari
- Department of Cardiology, School of Medicine, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Homa Taheri
- Department of Cardiology, School of Medicine, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mojtaba Fathi
- Department of Clinical Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Muhammad Javad Muhammadi
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reyhaneh Mahmoodian
- Endocrinology and Metabolism Center, Department of Internal Medicine, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Alborz, Iran
| | - Atieh Asgari
- Department of Cardiology, School of Medicine, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammadreza Tayaranian
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehdi Moharrami
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahsa Mahjani
- Department of Family Medicine, Alborz University of Medical Science, Karaj, Alborz, Iran
- General Practitioner, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bijan Ghobadian
- Endocrinology and Metabolism Research Centre, School of Medicine, Vali-e-Asr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Chiti
- Endocrinology and Metabolism Research Centre, School of Medicine, Vali-e-Asr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sheida Gohari
- Department of Systems Science and Industrial Engineering, State University of New York at Binghamton, Binghamton, NY, USA
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Govindarasu M, Abirami P, Rajakumar G, Ansari MA, Alomary MN, Aba Alkhayl FF, Aloliqi AA, Thiruvengadam M, Vaiyapuri M. Kaempferitrin inhibits colorectal cancer cells by inducing reactive oxygen species and modulating PI3K/AKT signalling pathway. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.02.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-Chloro-4-(3-Trifluoromethylphenylamino)-1H-Pyrrole-2,5-Dione Immobilized on Polymeric Poly (PEGMA-co-DMM) Carrier. Sci Pharm 2022. [DOI: 10.3390/scipharm90010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by its poor water solubility. In this study, the mechanisms of the antineoplastic action of MI-1 and its MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated by using the MTT and clonogenic assays, DNA intercalation with methyl green replacement, alkaline DNA comet assay, and Western-blot analysis. MI-1 compound and its MI-1/M5 complex possessed high toxicity towards colon (HCT116), cervical (HeLa) carcinoma cells and melanoma (SK-MEL-28) cells with GI50 value in a range of 0.75–7.22 µg/mL, and demonstrated high selectivity index (SI ˃ 6.9). The p53 status of colon cancer cells did not affect the sensitivity of these cells to the treatment with MI-1 and its MI-1/M5 complex. M5 polymer possessed low toxicity towards studied cells. The MI-1, MI-1/M5, and M5 only slightly inhibited growth of the pseudo-normal HaCaT and Balb/c 3T3 cell lines (GI50 ˃ 50 μg/mL). The MI-1 and its MI-1/M5 complex induced mitochondria-dependent pathway of apoptosis, damage of the DNA, and morphological changes in HCT116 cells, and affected the G2/M transition checkpoint. The MI-1 intercalated into the DNA molecule, while such capability of MI-1/M5 complex and M5 polymer was much lower. Thus, poly (PEGMA-co-DMM) might be a promising carrier for delivery of the maleimide derivative, MI-1, a novel kinase inhibitor, through improving its solubility in aqueous media and enhancing its antiproliferative action towards human tumor cells. Studies are in progress on the treatment of Nemeth-Kellner lymphoma (NK/Ly)-bearing mice with the MI-1 and MI-1/M5 complex.
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Maggiora G, Vogt M. Set-Theoretic Formalism for Treating Ligand-Target Datasets. Molecules 2021; 26:molecules26247419. [PMID: 34946500 PMCID: PMC8704321 DOI: 10.3390/molecules26247419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/16/2021] [Accepted: 12/03/2021] [Indexed: 11/20/2022] Open
Abstract
Data on ligand–target (LT) interactions has played a growing role in drug research for several decades. Even though the amount of data has grown significantly in size and coverage during this period, most datasets remain difficult to analyze because of their extreme sparsity, as there is no activity data whatsoever for many LT pairs. Even within clusters of data there tends to be a lack of data completeness, making the analysis of LT datasets problematic. The current effort extends earlier works on the development of set-theoretic formalisms for treating thresholded LT datasets. Unlike many approaches that do not address pairs of unknown interaction, the current work specifically takes account of their presence in addition to that of active and inactive pairs. Because a given LT pair can be in any one of three states, the binary logic of classical set-theoretic methods does not strictly apply. The current work develops a formalism, based on ternary set-theoretic relations, for treating thresholded LT datasets. It also describes an extension of the concept of data completeness, which is typically applied to sets of ligands and targets, to the local data completeness of individual ligands and targets. The set-theoretic formalism is applied to the analysis of simple and joint polypharmacologies based on LT activity profiles, and it is shown that null pairs provide a means for determining bounds to these values. The methodology is applied to a dataset of protein kinase inhibitors as an illustration of the method. Although not dealt with here, work is currently underway on a more refined treatment of activity values that is based on increasing the number of activity classes.
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Affiliation(s)
- Gerald Maggiora
- BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA
- Correspondence:
| | - Martin Vogt
- Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Friedrich-Hirzebruch-Allee 5-6, D-53115 Bonn, Germany;
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Kuznietsova H, Byelinska I, Dziubenko N, Lynchak O, Milokhov D, Khilya O, Finiuk N, Klyuchivska O, Stoika R, Rybalchenko V. Suppression of systemic inflammation and signs of acute and chronic cholangitis by multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione. Mol Cell Biochem 2021; 476:3021-3035. [PMID: 33792809 DOI: 10.1007/s11010-021-04144-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/23/2021] [Indexed: 12/12/2022]
Abstract
An aberrant activity of growth factor receptors followed by excessive cell proliferation plays a significant role in pathogenesis of cholangitis. Therefore, inhibition of these processes could be a fruitful therapeutic strategy. The effects of multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione (MI-1) on the hepatic and systemic manifestations of acute and chronic cholangitis in rats were addressed. MI-1 (2.7 mg/kg per day) was applied to male rats that experienced α-naphthylisothiocyanate-induced acute (3 days) or chronic (28 days) cholangitis. Liver autopsy samples, blood serum markers, and leukograms were studied. MI-1 localization in liver cells and its impact on viability of HepG2 (human hepatoma), HL60 (human leukemia), and NIH3T3 (normal murine fibroblasts) cell lines and lymphocytes of human peripheral blood (MTT, DNA fragmentation, DNA comet assays, Propidium Iodide staining) were assessed. Under both acute and chronic cholangitis, MI-1 substantially reduced liver injury, fibrosis, and inflammatory scores (by 46-86%) and normalized blood serum markers and leukograms. Moreover, these effects were preserved after a 28-day recovery period (without any treatment). MI-1 inhibited the HL60, HepG2 cells, and human lymphocytes viability (IC50 0.6, 9.5 and 8.3 µg/ml, respectively), while NIH3T3 cells were resistant to that. Additionally, HepG2 cells and lymphocytes being incubated with MI-1 demonstrated insignificant pro-apoptotic and pro-necrotic changes and DNA single-strand breaks, suggesting that MI-1 effects in liver might be partly caused by its cytotoxic action towards liver cells and lymphocytes. In conclusion, MI-1 attenuated the systemic inflammation and signs of acute and chronic cholangitis partly through cytotoxicity towards cells of hepatic and leukocytic origin.
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Affiliation(s)
- Halyna Kuznietsova
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
| | - Iryna Byelinska
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Natalia Dziubenko
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Oksana Lynchak
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Demyd Milokhov
- Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Olga Khilya
- Chemistry Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Nataliya Finiuk
- Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine
- Ivan Franko National University of Lviv, Lviv, Ukraine
| | - Olga Klyuchivska
- Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine
| | - Rostyslav Stoika
- Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
- Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine
- Ivan Franko National University of Lviv, Lviv, Ukraine
| | - Volodymyr Rybalchenko
- Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
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Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA. UKRAINIAN BIOCHEMICAL JOURNAL 2020. [DOI: 10.15407/ubj92.04.055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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Kuznietsova H, Dziubenko N, Herheliuk T, Prylutskyy Y, Tauscher E, Ritter U, Scharff P. Water-Soluble Pristine C 60 Fullerene Inhibits Liver Alterations Associated with Hepatocellular Carcinoma in Rat. Pharmaceutics 2020; 12:pharmaceutics12090794. [PMID: 32842595 PMCID: PMC7559840 DOI: 10.3390/pharmaceutics12090794] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/15/2020] [Accepted: 08/19/2020] [Indexed: 12/11/2022] Open
Abstract
Excessive production of reactive oxygen species is the main cause of hepatocellular carcinoma (HCC) initiation and progression. Water-soluble pristine C60 fullerene is a powerful and non-toxic antioxidant, therefore, its effect under rat HCC model and its possible mechanisms were aimed to be discovered. Studies on HepG2 cells (human HCC) demonstrated C60 fullerene ability to inhibit cell growth (IC50 = 108.2 μmol), to induce apoptosis, to downregulate glucose-6-phosphate dehydrogenase, to upregulate vimentin and p53 expression and to alter HepG2 redox state. If applied to animals experienced HCC in dose of 0.25 mg/kg per day starting at liver cirrhosis stage, C60 fullerene improved post-treatment survival similar to reference 5-fluorouracil (31 and 30 compared to 17 weeks) and inhibited metastasis unlike the latter. Furthermore, C60 fullerene substantially attenuated liver injury and fibrosis, decreased liver enzymes, and normalized bilirubin and redox markers (elevated by 1.7–7.7 times under HCC). Thus, C60 fullerene ability to inhibit HepG2 cell growth and HCC development and metastasis and to improve animal survival was concluded. C60 fullerene cytostatic action might be realized through apoptosis induction and glucose-6-phosphate dehydrogenase downregulation in addition to its antioxidant activity.
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Affiliation(s)
- Halyna Kuznietsova
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, Ukraine; (N.D.); (T.H.); (Y.P.)
- Correspondence: (H.K.); (U.R.); Tel.: +38-095-277-4370 (H.K.); +49-3677-69-3603 (U.R.)
| | - Natalia Dziubenko
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, Ukraine; (N.D.); (T.H.); (Y.P.)
| | - Tetiana Herheliuk
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, Ukraine; (N.D.); (T.H.); (Y.P.)
| | - Yuriy Prylutskyy
- Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Volodymyrska str., 64, 01601 Kyiv, Ukraine; (N.D.); (T.H.); (Y.P.)
| | - Eric Tauscher
- Institute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, Germany; (E.T.); (P.S.)
| | - Uwe Ritter
- Institute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, Germany; (E.T.); (P.S.)
- Correspondence: (H.K.); (U.R.); Tel.: +38-095-277-4370 (H.K.); +49-3677-69-3603 (U.R.)
| | - Peter Scharff
- Institute of Chemistry and Biotechnology, Technical University of Ilmenau, Weimarer str. 25, 98693 Ilmenau, Germany; (E.T.); (P.S.)
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Kuznietsova H, Dziubenko N, Byelinska I, Hurmach V, Bychko A, Lynchak O, Milokhov D, Khilya O, Rybalchenko V. Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety. J Drug Target 2019; 28:547-563. [PMID: 31814456 DOI: 10.1080/1061186x.2019.1703189] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs' action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes. PDs entered into electrostatic interactions with polar groups of phospholipid heads in cell membrane, and the power of interaction depended on the nature of PD radical substituents (greater for MI-1 and smaller for D1). Partial intercalation of MI-1 into the membrane hydrophobic zone also occurred. PDs concentrations induced apoptosis in malignant cells but normal ones had different sensitivity to those. MI-1 and D1 acted like antioxidants in inflamed colonic tissue, as evidenced by reduce of lipid and protein peroxidation products (by 43-67%) and increase of superoxide dismutase activity (by 40 and 58%) with restoring these values to control ones. MI-1 restored reduced haemoglobin and normalised elevated platelets and monocytes in settings of colorectal cancer, whereas D1 normalised only platelets. Thus, MI-1 and D1 could be used as competitive inhibitors of EGFR and VEGFR and antioxidants, which might contribute to realisation of their anti-inflammatory, proapoptotic and antitumor activity.
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Affiliation(s)
| | | | | | - Vasyl Hurmach
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Andriy Bychko
- Bogomolets National Medical University, Kyiv, Ukraine
| | - Oksana Lynchak
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Demyd Milokhov
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Olga Khilya
- Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
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Kuznietsova HM, Hurmach VV, Bychko AV, Tykhoniuk OI, Milokhov DS, Khilya OV, Volovenko YM, Rybalchenko VK. Synthesis and biological activity of 4-amino-3-chloro-1 H-pyrrole-2,5-diones. In Silico Pharmacol 2019; 7:2. [PMID: 31032168 DOI: 10.1007/s40203-019-0051-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 04/04/2019] [Indexed: 12/22/2022] Open
Abstract
4-Amino-3-chloro-1H-pyrrole-2,5-dione derivatives were designed and synthesized as potential tyrosine kinase inhibitors. One of them has been shown to inhibit growth of cancer cell lines and in vivo tumors. To determine the impact of side groups on biological activity the ability of different 4-amino-3-chloro-1H-pyrrole-2,5-diones to interact with ATP-binding domains of growth factor receptors and with model cell membranes were aimed to be discovered. The methods of molecular docking, short-molecular dynamics (in silico) and non-steady cyclic current-voltage characteristics (in vitro) were used. Five 4-amino-3-chloro-1H-pyrrole-2,5-diones were synthesized from 3,4-dichloro-1H-pyrrole-2,5-diones. All of them demonstrated the potential ability to form complexes with ATP-binding domains of EGFR and VEGFR2. These complexes were more stable compared to those with ANP. 4-Amino-3-chloro-1H-pyrrole-2,5-diones while interact with different bilayer lipid membranes caused an increase of their specific conductance and electric capacity, demonstrating the certain disturbance in lipid packing. Obtained data allowed us to suggest that proposed chemicals can interact with the surface of lipid bilayer, do likely intercalate into the membrane and form stable complexes with EGFR and VEGFR2. So, the prospect of developed chemicals to be effective EGFR and VEGFR2 inhibitors and therefore realize antitumor activity was concluded.
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Affiliation(s)
- Halyna M Kuznietsova
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
| | - Vasyl V Hurmach
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
| | - Andriy V Bychko
- 2Bogomolets National Medical University, 13, T. Shevchenko Blvd, Kiev, 01601 Ukraine
| | - Olena I Tykhoniuk
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
| | - Demyd S Milokhov
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
| | - Olga V Khilya
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
| | - Yulian M Volovenko
- 1Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska St., Kiev, 01601 Ukraine
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Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats. APPLIED NANOSCIENCE 2018. [DOI: 10.1007/s13204-018-0700-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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