Synthesis and structural depiction of the isomeric benzimidazole pair and  its in-silico anti-SARS-CoV-2 activities

Ananya Debnath; Shreya Mahato; Abhranil De; Himanshu Verma; Om Silakari; Bhaskar Biswas

doi:10.5155/eurjchem.15.1.39-49.2483

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Published: Mar 31, 2024

DOI: https://doi.org/10.5155/eurjchem.15.1.39-49.2483

Keywords:

Synthesis, MD simulations, Crystal structure, Molecular docking, Mono-substituted benzimidazole, In silico anti-SARS-COV-2 screening activity

Section

Research Article

Issue

Vol. 15 No. 1 (2024): March 2024

Dates

Received 2023-10-16
Accepted 2023-11-08
Published 2024-03-31

Ananya Debnath

Department of Chemistry, University of North Bengal, Darjeeling, 734013, India

https://orcid.org/0000-0001-9912-1133

Shreya Mahato

Department of Chemistry, University of North Bengal, Darjeeling, 734013, India

https://orcid.org/0000-0003-2266-9023

Abhranil De

Department of Basic Science and Humanities, Hooghly Engineering and Technology College, Hooghly 712103, India

https://orcid.org/0000-0003-2266-9023

Himanshu Verma

Molecular Modeling Laboratory, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India

https://orcid.org/0000-0003-2373-8940

Om Silakari

Molecular Modeling Laboratory, Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India

https://orcid.org/0000-0002-8314-7395

Bhaskar Biswas

Department of Chemistry, University of North Bengal, Darjeeling, 734013, India

https://orcid.org/0000-0002-5447-9729

Abstract

The present work presents a straightforward synthesis, spectroscopic and structural depiction, and in silico anti-SARS-CoV-2 activity of an isomeric monosubstituted benzimidazole pair, 2-(1H-benzo[d]imidazol-2-yl)-6-methoxyphenol (L₁O) and 4-(1H-benzo[d]imidazol-2-yl)-2-methoxyphenol (L₁P). The derivatives were synthesized by a coupling of aromatic aldehydes and o-phenylenediamine in ethanol under reflux. Different spectroscopic methods and X-ray structural analysis were employed to characterize the compounds. The crystal structure of L₁O reveals that the o-vanillin substituted benzimidazole compound crystallizes in a monoclinic system and adopts a planar geometry. In silico anti-SARS-CoV-2 proficiencies of synthetic derivatives were evaluated against the main protease (M^pro) and nonstructural proteins (nsp2 and nsp7) of SARS-CoV-2. Molecular docking reveals the binding scores for the L₁O-M^pro, L₁O-nsp2 and L₁O-nsp7 complexes as -11.31, -6.06 and -8.13 kcal/mol, respectively, while the binding scores for the L₁P-Mpro, L₁P-nsp2 and L1P-nsp7 complexes as -10.62, -5.09 and -6.91 kcal/mol, respectively, attributing the excellent conformational stability for both the isomeric benzimidazole derivatives.

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Debnath, A.; Mahato, S.; De, A.; Verma, H.; Silakari, O.; Biswas, B. Synthesis and Structural Depiction of the Isomeric Benzimidazole Pair and Its in-Silico Anti-SARS-CoV-2 Activities. Eur. J. Chem. 2024, 15, 39-49.

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