Alkylated Benzimidazoles: Design, Synthesis, Docking, DFT Analysis, ADMET Property, Molecular Dynamics and Activity Against HIV and YFV

Overview

Journal Comput Biol Chem

Publisher Elsevier

Date 2020 Oct 17

PMID 33068917

Citations 8

Authors

Ritika Srivastava

Sunil K Gupta

Farha Naaz

Parth Sarthi Sen Gupta

Madhu Yadav

Vishal Kumar Singh

Anuradha Singh

Malay Kumar Rana

Satish Kumar Gupta

Dominique Schols

Ramendra K Singh

Affiliations

Soon will be listed here.

Abstract

A series of alkylated benzimidazole derivatives was synthesized and screened for their anti-HIV, anti-YFV, and broad-spectrum antiviral properties. The physicochemical parameters and drug-like properties of the compounds were assessed first, and then docking studies and MD simulations on HIV-RT allosteric sites were conducted to find the possible mode of their action. DFT analysis was also performed to confirm the nature of the hydrogen bonding interaction of active compounds. The in silico studies indicated that the molecules behaved like possible NNRTIs. The nature - polar or non-polar and position of the substituent present at fifth, sixth, and N-1 positions of the benzimidazole moiety played an important role in determining the antiviral properties of the compounds. Among the various compounds, 2-(5,6-dibromo-2-chloro-1H-benzimidazol-1-yl)ethan-1-ol (3a) showed anti-HIV activity with an appreciably low IC value as 0.386 × 10μM. Similarly, compound 2b, 3-(2-chloro-5-nitro-1H-benzimidazol-1-yl) propan-1-ol, showed excellent inhibitory property against the yellow fever virus (YFV) with EC value as 0.7824 × 10μM.

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