Benzimidazole and Benzimidazole Derivatives as Anticancer Scaffolds: A Review of Synthetic Approaches

The objective of exploiting benzimidazole, a chemical compound with the molecular formula C7H6N2, varies depending on its application. In this review, articles published between 2001 and 2025 were analyzed. Its adaptability and multiple chemical properties make it valuable in fields such as pharmaceuticals, materials science, and chemical research. The structural characteristics of benzimidazole allow for a wide range of modifications and applications.

The benzimidazole derivatives were synthesized and analyzed. An extensive literature search was conducted using databases such as Google Scholar, PubMed, ScienceDirect, SpringerLink, Wiley Online Library, RSC Publishing, and Eureka Select. Key synthetic methods, including Philip's reaction, oxidative/reductive cyclization, multicomponent reactions, and microwave-assisted synthesis, were illustrated using ChemDraw Ultra.

This review outlines synthetic strategies for developing potent benzimidazole-based anticancer agents, highlighting their therapeutic potential through a summary of in vitro efficacy in inducing apoptosis and cell cycle arrest across various cancer cell lines.

Benzimidazole derivatives exhibit strong in vitro anticancer activity through apoptosis and cell cycle arrest, yet face challenges such as low bioavailability and limited clinical translation. The review highlights gaps in resistance mechanisms and delivery strategies, urging the use of in vivo studies, SAR-based optimization, and clinical advancement to realize their therapeutic potential.

The study highlights the chemical versatility of benzimidazole scaffolds and their structure-activity relationships in the design of anticancer drugs. Key findings emphasize efficient synthetic methodologies and functional modifications that enhance bioactivity. These insights contribute to the rational development of novel, potent anticancer agents, reinforcing the value of benzimidazoles in medicinal chemistry.