Hydrazone–heterocyclic hybrids as promising anticancer agents: a comprehensive review

Abstract

Hydrazones have gained significant attention in the field of medicinal chemistry because of their ease of preparation, crystalline nature, structural flexibility and broad-spectrum biological activity. Additionally, N-containing heterocycles have always contributed to anticancer drug discovery, with 73% of FDA-approved anticancer drugs based on them. Recently, the idea of hybrid drug design that synergistically combines two or more pharmacologically active molecules has become an effective strategy in discovering new anticancer drugs. Hence, combining two bioactive fragment hydrazones and N-containing heterocycles can be considered an effective strategy for discovering potent anticancer drugs. Among these, heterocycle–hydrazone hybrids derived from quinoline, indole, triazole, benzimidazole and isatin have displayed promising anticancer activities, with some of the studies even approaching in vivo evaluation. Overall, this review focuses on the anticancer activities of these hydrazone hybrids, their in vitro cytotoxic results, the proposed mechanism of action of the most active compound, cell death pathway results, docking studies, and cell cycle-arrest results. In addition, various synthetic strategies of hydrazones, including conventional methods, microwave and ultrasonication irradiation techniques, diazonium salt-derived methods and solvent-free reaction conditions, have been reported. Furthermore, the kinetics of hydrazone synthesis is described in brief.