Anticancer Potential of Chalcone Hybrids: Recent Advances in Hybrid Design and SAR Analysis

ABSTRACT Cancer treatment continues to face obstacles such as drug resistance and adverse effects, prompting increased interest in chalcone‐based hybrids as innovative therapeutic agents. Although several reviews on chalcone derivatives have been reported, a focused and comparative analysis of recently developed chalcone hybrids integrating diverse heterocyclic and pharmacophoric motifs, along with their mechanistic and structure–activity relationship (SAR) trends, remains limited. In this context, the present review summarizes advances in chalcone‐based hybrid molecules reported over the past five years, with particular emphasis on hybrids containing bioactive scaffolds such as benzofuran, pyrimidine, triazole, indole, and related heterocyclic systems. The review comparatively discusses how hybridization strategies influence anticancer potency, selectivity, and multitarget activity through mechanisms including tubulin polymerization inhibition, kinase modulation, topoisomerase inhibition, apoptosis induction, and DNA interaction. Furthermore, cross‐comparison among different hybrid classes is presented to identify consistent structural trends governing cytotoxic activity. By critically evaluating recent SAR findings and mechanistic insights, this review provides a broader understanding of the design principles underlying chalcone hybrid therapeutics and highlights future directions for the rational development of more effective and selective anticancer agents.