Benzimidazole: A Multifacted Nucelus for Anticancer Agents

Cancer is characterized by an uncontrolled proliferation of cells, dedifferentiation, invasiveness and metastasis. Endothelial growth factor (eGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), checkpoint kinase 1 & 2 ( Chk1 & Chk2), aurora kinases, topoisomerases, histone deacetylators (HDAC), poly(ADP-Ribose)polymerase (PARP), farnesyl transferases, RAS-MAPK pathway and PI3K-Akt-mTOR pathway, are some of the prominent mediators implicated in the proliferation of tumor cells. Huge artillery of natural and synthetic compounds as anticancer, which act by inhibiting one or more of the enzymes and/or pathways responsible for the progression of tumor cells, is reported in the literature. The major limitations of anticancer agents used in clinics as well as of those under development in literature are normal cell toxicity and other side effects due to lack of specificity. Hence, medicinal chemists across the globe have been working for decades to develop potent and safe anticancer agents from natural sources as well as from different classes of heterocycles. Benzimidazole is one of the most important and explored heteronucelus because of their versatility in biological actions as well as synthetic applications in medicinal chemistry. The structural similarity of amino derivatives of benzimidazole with purines makes it a fascinating nucleus for the development of anticancer, antimicrobial and anti-HIV agents. This review article is an attempt to critically analyze various reports on benzimidazole derivatives acting on different targets to act as anticancer so as to understand the structural requirements around benzimidazole nucleus for each target and enable medicinal chemists to promote rational development of antitumor agents.