Functionalized Benzimidazole Scaffolds: Privileged Heterocycle for Drug Design in Therapeutic Medicine

Abstract

Benzimidazole derivatives are crucial structural scaffolds found in diverse libraries of biologically active compounds which are therapeutically useful agents in drug discovery and medicinal research. They are structural isosteres of naturally occurring nucleotides, which allows them to interact with the biopolymers of living systems. Hence, there is a need to couple the latest information with the earlier documentations to understand the current status of the benzimidazole nucleus in medicinal chemistry research. This present work unveils the benzimidazole core as a multifunctional nucleus that serves as a resourceful tool of information for synthetic modifications of old existing candidates in order to tackle drug resistance bottlenecks in therapeutic medicine. This manuscript deals with the recent advances in the synthesis of benzimidazole derivatives, the widespread biological activities as well as pharmacokinetic reports. These present them as a toolbox for fighting infectious diseases and also make them excellent candidates for future drug design.

Facile Synthesis, Characterization and <i>in vitro</i> Antibacterial Efficacy of Functionalized 2-Substituted Benzimidazole Motifs

“…Benzimidazole is a benzo-fused imidazole known to be highly versatile heterocyclic compounds in therapeutic medicine, agrochemicals, and catalysis study. In furtherance of our quest to design and evaluate the biological activity of benzimidazole motifs [2,20], we have herein synthesized novel functionalized benzimidazole scaffolds so as to unveil the antibacterial potential for probable future drug discovery. First, condensation reaction of o-phenylenediamine (o-PDA) on the COOH functionality of cheap and readily available amino acid, L-leucine was carried out in ethanol solvent using the catalytic amount of ammonium chloride (NH 4 Cl) as an eco-friendly medium, as shown in Scheme 1, which was according to our recently reported procedure [20].…”

“…Over the years, heterocyclic compounds have been reported to be biomimetically-useful and pharmacophorically-sensitive frameworks with high essentiality in accessing biomolecular drugs and drug-like candidates in drug design [1]. One of the N-heterocyclic templates of high diversity in the pharmacological adventure are benzimidazole motifs, and they are known to be unavoidable rubrics in high through screening and identification of valuable lead targets in therapeutic research [2]. They possess observable biochemical interaction with many biomolecules in the body system because of their structural resemblance to some naturally existing nucleotides [3].…”

Microwave‐assisted synthesis of 1‐substituted‐1H‐benzimidazolium salts: Non‐competitive inhibition of human carbonic anhydrase I and II

“…Many benzimidazole‐based commercial drugs were developed thanks to anticancer, antihelmintic, antifungal, and antiulcer properties of benzimidazole derivatives. Additionally, some benzimidazole derivatives performed remarkable antibacterial, antioxidant, anticonvulsant, anti‐inflammatory, and anti‐HIV activities . Benzimidazole derivatives exhibit anticancer effects by enzyme inhibition or DNA intercalation .…”

Antimicrobial Activity of Thiocarbohydrazones: Experimental Studies and Alignment‐Independent 3D QSAR Models

“…The reason for testing any potentially promising new group of antimicrobial agents is constituted by the alarming and rapidly increasing spread of various pathogens that are resistant to previously known clinically useful antimicrobial drugs. Due to the great importance in pharmacology and agriculture, heterocyclic compounds receive increasing attention . Special attention is taken in getting nitrogen‐based heterocyclic compounds, and hydrazones are of great interest to researchers because of their diverse biological and clinical applications .…”