Benzimidazole derivatives as anticancer agents: a comprehensive review of their synthesis, mechanism, and clinical potential

Benzimidazole derivatives represent a versatile class of compounds in anticancer drug development due to their unique fused bicyclic structure comprising benzene and imidazole rings. The derivatives are engineered to include various chemical modifications, where in most cases, they include other heterocyclic rings or pharmacophores which augment their biological activities and specificity to cancer cells. These anticancer effects are complex and encompass Tubulin polymerization inhibition, DNA intercalation, topoisomerases I and II suppression, apoptotic pathway modulation, and inhibition of major tumor suppressor kinases that include the MAPK and PI3K/AKT. Such activities interfere with the growth of cancer cells, cause cell cycle arrest, induce apoptosis, and prevent angiogenesis and metastasis. Their <i>in vitro</i> antitumor and <i>in vivo</i> efficacies that include the ability to be used to treat a variety of tumor cell lines in preclinical studies are affirmed by their cytotoxicity and have potential pharmacokinetic and safety profiles. This group of compounds have great clinical potential in the form of targeted therapeutics because of structural flexibility making them useful in precision medicine. Their progression into a clinically useful anticancer drug remains investigating of their structure-activity relationship and molecular docking studies, with benzimidazole derivatives being some of the possible real-life solutions against cancer.