Flavonoids and Their Derivatives as DNA Topoisomerase Inhibitors with Anti-Cancer Activity in Various Cell Models: Exploring a Novel Mode of Action

Flavonoids, a diverse group of plant-derived secondary metabolites, have garnered significant attention for their potential anti-cancer properties. This review explores the role of flavonoids as inhibitors of DNA topoisomerases, key enzymes essential for DNA replication, transcription, and cell division. The article offers a comprehensive overview of flavonoid classification, biosynthesis, and their widespread natural occurrence. It further delves into the molecular mechanisms through which flavonoids exert their anti-cancer effects, emphasizing their interactions with topoisomerases. The review provides a thorough analysis of both in vitro and in vivo studies that highlight the topoisomerase inhibitory activities of various flavonoids and their derivatives. Key findings demonstrate that flavonoids can function as catalytic inhibitors, poisons, or DNA intercalators, affecting both type I and type II topoisomerases. The structure-activity relationships of flavonoids concerning their topoisomerase inhibitory potency are also examined. This review underscores the potential of flavonoids as promising lead compounds for the development of novel topoisomerase inhibitors, which could have important implications for cancer therapy. However, it also acknowledges the need for further research to fully understand the intricate interactions between flavonoids and topoisomerases within the cellular environment.