Advances in chalcone derivatives: Unravelling their anticancer potential through structure-activity studies

Abstract

Cancer continues to be a global health challenge, thereby necessitating the evolution of innovative therapeutic strategies. The synthesis of chalcone derivatives has garnered significant attention in the field of anticancer research due to their potential as effective therapeutic agents. This review presents a comprehensive analysis of recent developments in the synthesis of chalcone derivatives as anticancer agents. A systematic examination of potent chalcone derivatives, their in-silico studies (if any) and methods of anticancer activity evaluation has been carried out. Furthermore, an in-depth analysis of SAR studies has been presented in figures, to explore the crucial structural modifications resulting in enhanced anticancer activity. Chalcone derivatives have undergone extensive investigation for their effectiveness in targeting the MCF-7 (breast), A549 (lung), HepG2 (liver), and HCT-116 (colorectal) cancer cell lines. Heterocyclic chalcone derivatives, specifically those incorporating five or more heteroatoms (N, S) in their structures, displayed significantly enhanced anticancer activity against the MCF-7 cell line. These compounds primarily targeted the tubulin protein, followed by the epidermal growth factor receptor (EGFR), topoisomerase, and other pertinent proteins at the molecular level. Among these derivatives, those bearing quinazoline and pyrazole showed the highest potency with IC50 values below 0. 01 µM against MCF-7. Conversely, chalcone derivatives bearing imidazole exhibited comparatively lower anticancer activity across the tested cell lines.Lastly, the potential challenges and future avenues in the development of chalcone derivatives as prospective anticancer candidates, are also discussed. In summary, preclinical studies indicate that chalcone derivatives show promise as versatile anticancer agents, warranting comprehensive further research to fully understand and harness their potential.