Imidazopyridine Scaffold as an Effective Tubulin Polymerization Inhibitor

Abstract

Tubulin and the tubulin cycle, which have many vital cellular functions in living cells, are privileged targets for the development of anticancer drug candidates. In the processing of cellular processes, especially cell division, alpha and beta tubulin polymerize to form microtubules and continue the cycle by depolymerizing again. Disruption of the polymerization-depolymerization dynamics of microtubules by various agents causes mitotic cell arrest and subsequent cell death via apoptosis. This review summarizes the tubulin cycle, cancer, and target regions. Tubulin has three main target binding sites: taxane, vinca, and colchicine. In particular, the colchicine binding site, which is the current target for disrupting the tubulin cycle, is inhibited by various synthetic compounds, and the common properties of these compounds are emphasized. The results show that highly effective cytotoxic agents can be developed by modifying the imidazopyridine scaffold, which remains open to exploration. The remarkable antitubulin and cytotoxic effects of recently developed compounds with an imidazopyridine ring are interesting. A detailed report of anti-tubulin agents with imidazopyridine structures, among the tubulin polymerization inhibitors developed to date, and an evaluation of the structure-activity relationship is presented here. In addition, the new molecular topology established in this review based on the structure-activity relationships of imidazopyridine will inspire research groups to develop new imidazopyridine-based anti-tubulin agents with clinical anticancer potential in the near future.