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Design and synthesis of heterocyclic azole based bioactive compounds: Molecular structures, quantum simulation, and mechanistic studies through docking as multi-target inhibitors of SARS-CoV-2 and cytotoxicity.
Haribabu, Jebiti; Garisetti, Vasavi; Malekshah, Rahime Eshaghi; Srividya, Swaminathan; Gayathri, Dasararaju; Bhuvanesh, Nattamai; Mangalaraja, Ramalinga Viswanathan; Echeverria, Cesar; Karvembu, Ramasamy.
  • Haribabu J; Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
  • Garisetti V; Facultad de Medicina, Universidad de Atacama, Los Carreras 1579, 1532502 Copiapo, Chile.
  • Malekshah RE; Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India.
  • Srividya S; Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
  • Gayathri D; Department of Chemistry, Iran University of Science and Technology, Tehran 16846‒13114, Iran.
  • Bhuvanesh N; Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India.
  • Mangalaraja RV; Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India.
  • Echeverria C; Department of Chemistry, Texas A & M University, College Station, TX 77842, USA.
  • Karvembu R; Advanced Ceramics and Nanotechnology Laboratory, Department of Materials Engineering, Faculty of Engineering, University of Concepcion, Concepcion, Chile.
J Mol Struct ; 1250: 131782, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1474901
ABSTRACT
Two heterocyclic azole compounds, 3-(2,3-dihydrobenzo[d]thiazol-2-yl)-4H-chromen-4-one (SVS1) and 5-(1H-indol-3-yl)-4-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (SVS2) were obtained unexpectedly from 2-aminothiophenol and 4-oxo-4H-chromene-3-carbaldehyde (for SVS1), and (E)-2-((1H-indol-3-yl)methylene)-N-methylhydrazine-1-carbothioamide in the presence of anhydrous FeCl3 (for SVS2), respectively. The compounds were well characterized by analytical and spectroscopic tools. The molecular structures of both the compounds were determined by single crystal X-ray diffraction (XRD) study. The results obtained from density functional theory (DFT) study revealed the molecular geometry and electron distribution of the compounds, which were correlated well with the three-dimensional structures obtained from the single crystal XRD. DMol3 was used to calculate quantum chemical parameters [chemical potential (µ), global hardness (η), global softness (σ), absolute electronegativity (χ) and electrophilicity index (ω)] of SVS1 and SVS2. Molecular docking study was performed to elucidate the binding ability of SVS1 and SVS2 with SARS-CoV-2 main protease and human angiotensin-converting enzyme-2 (ACE-2) molecular targets. Interestingly, the binding efficiency of the compounds with the molecular targets was comparable with that of remdesivir (SARS-CoV-2), chloroquine and hydroxychloroquine. SVS1 showed better docking energy than SVS2. The molecular docking study was complemented by molecular dynamics simulation study of SARS-CoV-2 main protease-SVS1 complex, which further exemplified the binding ability of SVS1 with the target. In addition, SVS1, SVS2 and cisplatin were assessed for their cytotoxicity against a panel of three human cancer cells such as HepG-2 (hepatic carcinoma), T24 (bladder) and EA.hy926 (endothelial), as well as Vero (kidney epithelial cells extracted from an African green monkey) normal cells using MTT assay. The results showed that SVS2 has significant cytotoxicity against HepG-2 and EA.hy926 cells with the IC50 values of 33.8 µM (IC50 = 49.9 µM-cisplatin and 8.6 µM-doxorubicin) and 29.2 (IC50 = 26.6 µM-cisplatin and 3.8 µM-doxorubicin), respectively.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: J Mol Struct Year: 2022 Document Type: Article Affiliation country: J.molstruc.2021.131782

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: J Mol Struct Year: 2022 Document Type: Article Affiliation country: J.molstruc.2021.131782