One‐pot synthesis of novel benzimidazoles with a naphthalene moiety as antimicrobial agents and molecular docking studies

Abstract

In an attempt to design a greener approach for the synthesis of a potent class of antimicrobials, 1,2‐phenylenediamine derivatives were reacted with various 1/2‐carboxylic acid‐substituted naphthalene derivatives to generate a series of naphthyl‐substituted benzimidazole derivatives (11–19) using polyphosphoric acid as catalyst under microwave irradiation and conventional synthesis method. This is an eco‐friendly and swift reaction method for a synthetic approach to diverse benzimidazoles. Structures of the synthesized compounds were established on the basis of spectral data and they were screened for their antimicrobial activity. Compound 18 showed maximum potency against all Gram‐positive and Gram‐negative bacterial strains with a minimum inhibitory concentration (MIC) value in the range of 7.81–62.50 μg/ml. Only compound 17 was found to be the most active against all fungal strains with a MIC value of 15.62 μg/ml. In this study, we performed molecular docking experiments to understand the interactions between compounds 17 and 18 and E. coli topoisomerase I, and we compared the results obtained with that of 2‐(3,4‐dimethoxyphenyl)‐5‐[5‐(4‐methylpiperazin−1‐yl)‐1H‐benzimidazol‐2‐yl]‐1H‐benzimidazole (DMA). Compounds 17 and 18 demonstrated strong interactions with important active site residues, similar to DMA. As a result, the compounds obtained from this study can be used in designing new potent inhibitors of E. coli topoisomerase I.

Exploring the Versatility of Benzimidazole Scaffolds as Medicinal Agents: A Brief Update

“…The derivatives are effective against drug-resistant Mtb and some possess a bactericidal approach. The synthesis of naphthyl-substituted benzimidazole derivatives ( 88) and ( 89) was reported by Ersan et al in 2020 [77]. The antimicrobial activity was screened and was found that (89) showed maximum potency against all gram-positive and gram-negative bacteria.…”

2-Phenyl substituted Benzimidazole derivatives: Design, synthesis, and evaluation of their antiproliferative and antimicrobial activities

“…Among the nitrogen-containing compounds, benzazoles (benzimidazole, benzoxazole, and benzothiazole, etc.) are a subject of great interest to our research group for investigating drug development due to their known pharmacological and biological activities [2][3][4][5][6][7][8][9][10][11]. Benzimidazole is primarily de ned as a privileged substructure in terms of purine-like scaffold feature and its ability to interact with various unrelated molecular targets [12,13].…”

Theoretical Determination of Corrosion Inhibitor Activities of Naphthalene and Tetralin

“…It is very volatile and burns with a smoky flame [1]. There are some drugs containing naphthalene, such as nafcillin, naftifine, tolnaftate, and terbinafine [2], which play a crucial role in the management of microbial infections. Naphthalene mono hydroxide derivatives are called naphthol [3,4].…”