Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)

Abstract

Cancer, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth, remains a prominent cause of death across the world. Almost all currently available anticancer agents used in clinical practice have developed multidrug resistance, creating an urgent need to develop novel chemotherapeutics. Benzimidazole derivatives could exert anticancer properties through diverse mechanisms, inclusive of the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, antiangiogenesis, and blockage of glucose transport. Moreover, several benzimidazole-based agents have already been approved for the treatment of cancers. Hence, benzimidazole derivatives are useful scaffolds for the development of novel anticancer agents. In particular, benzimidazole hybrids could exert dual or multiple antiproliferative activities and had the potential to overcome drug resistance, demonstrating the potential of benzimidazole hybrids as potential prototypes for clinical deployment in the control and eradication of cancers. The purpose of the present review article is to provide a comprehensive landscape of benzimidazole hybrids as potential anticancer agents, and the structure-activity relationship as well as mechanisms of action are also discussed to facilitate the further rational design of more effective candidates, covering articles published from 2019 to 2021.

Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking

“…The subG0/G1 peak is indicative of DNA fragmentation and suggests that the cells are dying, most likely through apoptosis. The arrest of the cell cycle in the G2/M phase in the cells treated with the various benzimidazole derivatives has also been observed in several recently published studies [ 41 ].…”

Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents

“…Safety profile of compound 6c , as a cytotoxic agent, was investigated towards normal cells, human normal embryonic kidney cells (HEK-293), in comparison to a reference drug, staurosporine 42 , 43 . As displayed in Table 4 , compound 6c exhibited better safety by reporting lower cytotoxicity against the normal cell (HEK-293), IC 50 = 53.69 μM compared to staurosporine, IC 50 = 35.33 μM.…”

Design, Synthesis, and Structural Insights of a Series of Zn(II)–NSAID Based Coordination Complex Derived Metallogels and Their Plausible Applications in Self Drug Delivery

“…Benzimidazole derivatives are often bioactive and show anticancer properties . Many NSAIDs are known anticancer agents. , We, therefore, considered the benzimidazole derivatives BZ and PBZ as coligands to synthesize a series of CCs from a number of NSAIDs and Zn­(NO 3 ) 2 .…”