Heterocyclic molecules are crucial in organic chemistry, and benzimidazoles, with their intricate structure and adaptability, are especially significant in the field of medicinal chemistry. This review provides an overview of benzimidazole chemistry, including its basic properties, synthetic procedures, and numerous biological applications. Benzimidazole nucleus, derived from the fusion of a benzene ring with imidazole, has been known since 1944 for its biological importance, structural similarities to purines, and its capability to interact with proteins and modulate biochemical processes. Different synthetic approaches for benzimidazole derivatives, primarily based on o-phenylenediamine, have also been systematically classified in this review. These methodologies involve reactions with carboxylic acids (Phillips method, ammonium chloride catalysis, microwave irradiation, polyphosphoric acid-assisted reflux, and ZnO nanoparticles-assisted green synthesis), aldehydes (oxygen molecular oxidation, iodine catalysis, sodium metabisulfite, ferric hydrogensulfate, sodium hexafluoroaluminate, dioxanedibromide, SDS-assisted synthesis, palladium/copper catalysis, copper(II) hydroxide, tert-butyl nitrite, solvent-free methods, boric acid catalysis, PEG-400, and lactic acid), Lewis acid, anhydride, ketone, orthoester, acid chloride, cyanogen bromide, orthoformate, ester, and nitrile. Special attention is paid to the green chemistry revolution across processes and methods, with environmentally friendly, benign solvents, catalysts, and synthetic plans that have reduced environmental impact. The review also highlights the wide range of biological activities of benzimidazole derivatives and their potential in drug discovery. These biological activities consist of excellent antibacterial activities against Gram+ and Gram- bacteria, strong anticancer activities against different cell lines and enzymes (e.g., DNA topoisomerase I, sirtuin enzymes), and remarkable antiviral activities against a set of viruses such as HIV and TMV. Moreover, BZDs demonstrate anti-inflammatory and analgesic, antifungal, antioxidant, antidiabetic (α-amylase, α-glucosidase suppression), antiprotozoal ( Trichinella spiralis and Giardia lamblia parasites), antihypertensive (ACE inhibitors and AT₁ antagonists), anticoagulant (thrombin inhibitory), and antidepressant effects (GSK-3β inhibitors). The report highlights the therapeutic potential of the benzimidazole framework as a promising lead for new drug design based on a large number of biological and clinical studies.
Almohammdi et al. (Tue,) studied this question.