Benzimidazole, a fused bicyclic compound with benzene and pentacyclic 1,3-diazole moeities, has a simple aromatic heterocyclic structure. The moiety has become an indispensable anchor for the development of new pharmacologically active products, and has yielded several therapeutic agents with anticancer, antihypertensive, antimicrobial, antifungal and antiulcer effects. Benzimidazoles, as synthetically feasible and pharmacophoric synthons, have been relentlessly pursued for the preparation of new analogues and derivatives, and they have successfully developed into some of the most sought-after and vital pharmacophores for drug discovery. The use of varied substituents and differing patterns around the benzimidazole nucleus has provided a wide spectrum of biological activities. In addition, the benzimidazole moiety constitutes a building block for the production of several drugs, drug candidates, new chemical entities, and lead molecules. The importance of this nucleus for bioactivity, e.g., antibacterial, antitubercular, antidiabetic, anticancer, antifungal, anti-inflammatory, analgesic, antioxidant, antihistaminic, and antimalarial activity, has led us to take note and provide an overview of the synthetic development approaches for various benzimidazole derivatives together with their biological actions. This review is projected to further assist in the design and development of new benzimidazole-based compounds for new and optimized pharmacologically active products towards new drug-development strategies.

A novel series of benzimidazole ureas 3a–h were elaborated using 2-(1H-benzoimidazol-2-yl) aniline 1 and the appropriate isocyanates 2a–h. The antioxidant and possible antidiabetic activities of the target benzimidazole-ureas 3a–h were evaluated. Almost all compounds 3a–h displayed strong to moderate antioxidant activities. When tested using the three antioxidant techniques, TAC, FRAP, and MCA, compounds 3b and 3c exhibited marked activity. The most active antioxidant compound in this family was compound 3g, which had excellent activity using four different methods: TAC, FRAP, DPPH-SA, and MCA. In vitro antidiabetic assays against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds tested had good to moderate activity. The most favorable results were obtained with compounds 3c, 3e, and 3g, and analysis revealed that compounds 3c (IC₅₀ = 18.65 ± 0.23 μM), 3e (IC₅₀ = 20.7 ± 0.06 μM), and 3g (IC₅₀ = 22.33 ± 0.12 μM) had good α-amylase inhibitory potential comparable to standard acarbose (IC₅₀ = 14.21 ± 0.06 μM). Furthermore, the inhibitory effect of 3c (IC₅₀ = 17.47 ± 0.03 μM), 3e (IC₅₀ = 21.97 ± 0.19 μM), and 3g (IC₅₀ = 23.01 ± 0.12 μM) on α-glucosidase was also comparable to acarbose (IC₅₀ = 15.41 ± 0.32 μM). According to in silico molecular docking studies, compounds 3a–h had considerable affinity for the active sites of human lysosomal acid α-glucosidase (HLAG) and pancreatic α-amylase (HPA), indicating that the majority of the examined compounds had potential anti-hyperglycemic action.