In silico anti-SARS-CoV-2 activities of five-membered heterocycle-substituted benzimidazoles

•Design and synthesis of a series of hetero-cycle substituted benzimidazoles.•Straightforward and green-synthetic route.•SARS-CoV-2 screening activities against main protease and non-structural proteins.•X-ray structure of the thiophene-substituted benzimidazole. The manuscript deals with cost-effec...

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Veröffentlicht in:Journal of molecular structure 2022-08, Vol.1261, p.132869-132869, Article 132869
Hauptverfasser: Mudi, Prafullya Kumar, Mahato, Rajani Kanta, Verma, Himanshu, Panda, Subhra Jyoti, Purohit, Chandra Sekhar, Silakari, Om, Biswas, Bhaskar
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Sprache:eng
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Zusammenfassung:•Design and synthesis of a series of hetero-cycle substituted benzimidazoles.•Straightforward and green-synthetic route.•SARS-CoV-2 screening activities against main protease and non-structural proteins.•X-ray structure of the thiophene-substituted benzimidazole. The manuscript deals with cost-effective synthesis, structural characterization and in silico SARS-CoV-2 screening activity of 5-membered heterocycle-substituted benzimidazole derivatives, 1-((1H-pyrrol-2-yl)methyl)-2-(1H-pyrrol-2-yl)-1H-benzo[d]imidazole (L1), 2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzo[d]imidazole (L2), 2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole (L3). The benzimidazole compounds were synthesized through a green-synthetic approach by coupling of 5-membered heterocyclic-carboxaldehyde and o-phenylenediamine in water under an aerobic condition. The compounds were characterized by various spectroscopic methods and X-ray structural analysis. The suitable single-crystals of the methyl derivative of L3 were grown as L3′ which crystallized in a monoclinic system and the thiophene groups co-existed in a nearly a perpendicular orientation. Further, in silico anti-SARS-CoV-2 proficiency of the synthetic derivatives is evaluated against main protease (Mpro) and non-structural proteins (nsp2 and nsp7) of SARS-CoV-2. Molecular docking and molecular dynamics analysis of the ligands (L1-L3) against Mpro and nsp2 and nsp7 for 50 ns reveal that L3 turns out to be the superlative antiviral candidate against Mpro, nsp2 and nsp7 of SARS-CoV-2 as evident from the binding score and stability of the ligand-docked complexes with considerable binding energy changes. [Display omitted]
ISSN:0022-2860
1872-8014
DOI:10.1016/j.molstruc.2022.132869