Preferential Synthesis and Pharmacological Evaluation of Mono‐ and Di‐substituted Benzimidazole Derivatives

Abstract

A series of substituted benzimidazoles were synthesized by condensing o-phenylenediamine with aromatic aldehydes in water using surfactants as catalyst. Mono and disubstituted benzimidazoles were formed preferentially with benzalkonium chloride and sodium dodecyl sulfate respectively. In silico molecular docking study revealed that 1-(4-chlorobenzyl)-2-(4chlorophenyl)-1H-benzo [d]imidazole bound strongly with delta, mu and kappa opioid receptors with binding scores of À 9.4, À 8.7 and À 9.9 Kcal/mol respectively. This derivative also possessed highest binding (À 9.0 Kcal/mol) against tubulin (binding score of albendazole was À 6.4 Kcal/mol). The molecule also showed potential antibacterial activity with MIC 50 ranging 16-128 μg/ml in in vitro antibacterial assay. Two benzimidazole derivatives showed powerful interaction with cyclooxygenase-1 and cyclooxygenase-2 (À 8.1 and À 8.9 Kcal/ mol respectively) indicating their high analgesic and antiinflammatory potentials. All the compounds produced significant binding (À 5.2 to À 8.2 Kcal/mol) towards urate oxidase, glutathione reductase and peroxiredoxin. Monosubstituted derivative 4-(1H-benzo[d]imidazol-2-yl)phenol displayed superior binding (À 6.5 Kcal/mol) with glucosamine 6-phosphate synthase compared to ciprofloxacin (À 6.3 Kcal/mol). In PASS analysis, monosubstituted derivatives demonstrated significant drug-like potential (Pa > 0.7). Hence, the synthesized benzimidazole derivatives can be used as potential leads for developing new drugs.

Benzimidazol‐1‐yl‐1‐phenylpropanone Analogs as Potent Antimicrobial Agents: Rational Design and Synthesis

“…[4] Later, some of the in-silico studies were performed from which the inference has been drawn that 2 and 3 position of the benzimidazole substitution and their derivatives own the tremendous pharmacological effects. [5] Likewise, the studied molecules were known to possess the anti-ulcer, [6] antineoplastic [7] and anti-inflammatory activities [8] etc. Moreover, some of the Schiff bases were also explored and have been reported to carry the notable therapeutic profile.…”

“…Despite this fact, innumerable bids have been done in the same discipline, nevertheless the substituted benzimidazole derivatives have come out as the promising and potential candidate processing the sustained capacity for the inhibition of microbial growth [4] . Later, some of the in‐silico studies were performed from which the inference has been drawn that 2 and 3 position of the benzimidazole substitution and their derivatives own the tremendous pharmacological effects [5] . Likewise, the studied molecules were known to possess the anti‐ulcer, [6] anti‐neoplastic [7] and anti‐inflammatory activities [8] etc.…”