First-row transition metal compounds containing benzimidazole ligands: An overview of their anticancer and antitumor activity

Cancer can be defined as an irregular functioning of the cell cycle that results in a progressive loss of cell differentiation and uncontrolled cell growth. Moreover, despite countless research advances in prevention and therapy, cancer remains one of the leading causes of death worldwide. Besides surgery, radiotherapy and immunotherapy, chemotherapy is one of the most effective methods for cancer treatment. However, in many cases, commercial chemotherapeutic agents suffer of limited efficacy and serious side effects. In addition, major chemotherapy treatments often experience major hurdles, being multi-drug resistance (MDR) the biggest obstacle. Hence, major efforts have been devoted to the design of new anticancer drugs with enhanced efficacy against cancer cells with minimum side effects. Some of these commercial drugs include benzimidazole moieties on their structures, for instance abemaciclib, bendamustine, crenolanib, dovitinib, galeterone, glasdegib, liarozole, nocodazole, pracinostat, selumetinib, veliparib, among others. Thus, this manuscript reviews the in vitro anticancer and antitumor activity of the first-row transition metal compounds containing benzimidazole-based ligands on their structures. Factors such as the effect of ligand type, metal centre, molecular structure and geometry on biological activity were analysed; and the relevance of the first-row transition metals in the health area was discussed, including the different assays used in the determination of their cytotoxic activity. We hope that this review may serve to further stimulate and advance the design of novel metal coordination compounds including first-row transition metals and the use of benzimidazole ligands as an ideal combination to produce very active, yet selective potent metallodrugs.