A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives.

Shejuti Rahman Brishty,Mayeen Uddin Khandaker,S M Abdur Rahman,Md Jamal Hossain,Hamid Osman,Mohammad Rashed Iqbal Faruque

doi:10.3389/fphar.2021.762807

Abstract

Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

Highlights

Benzimidazole, alternatively known as 1H-benzimidazole and 1,3-benzodiazole, consists of benzene ring fused with a five-membered imidazole ring, and is an important heterocyclic pharmacophore
Lingyun Zhang, et al benzimidazole derivatives that showed inhibition of voltage gated sodium channel, which might be promising in the treatment of various (Continued on following page)
Rathore et al (Rathore et al, 2017) synthesized a series of 1-{(5-substituted-1,3,4-oxadiazol-2yl)methyl}-2-(morpholinomethyl)-1H-benzimidazole derivatives (152–154) and reported that the compound 152 having chloro group at the ortho position of phenyl ring showed promising antiinflammatory effect compared to standard indomethacin (74.17 ± 1.28% vs. 57.79 ± 1.71%)

Summary

INTRODUCTION

Benzimidazole, alternatively known as 1H-benzimidazole and 1,3-benzodiazole, consists of benzene ring fused with a five-membered imidazole ring, and is an important heterocyclic pharmacophore. Through the course of many years of research, benzimidazole has emerged as an important heterocyclic system because of its existence in diverse biologically active compounds, such as antiparasitics, antimicrobials, antivirals, antifungals, anticonvulsants, antihypertensives, antihistaminics, analgesics, antiinflammatory agents, anticancers, anticoagulants and proton pump inhibitors (Figure 1) (Fei and Zhou, 2013; Wang et al, 2015). Compound 17 containing chloro group displayed the most remarkable antifungal activity, with MIC values in the range of 25–62.5 μg/ml against three fungal strains compared to standard ketoconazole (MIC 50 μg/ml). A library of 1-methyl-N-[(substituted-phenylmethylidene)1H-benzimidazol-2-amines (20–24) were synthesized and reported for notable antimicrobial activity against Grampositive S. aureus (ATCC 6538), B. pumilus (ATCC 14884) and Gram-negative E. coli (NCTC 10418), P. aeruginosa (ATCC 25619) bacteria compared to reference drug ampicillin (Noolvi et al, 2014).

WO2018057810A1 Chandrasekhar France

12 US 20150322065A1 Chappie et al United States Azabenzimidazole

CONCLUSION