Recent Advances in the Synthesis and Biological Applications of Chalcone Derivatives: A Comprehensive Review

Chalcones are a versatile class of natural and synthetic compounds that have attracted considerable attention because of their simple chemical structure, synthetic accessibility, and broad spectrum of biological activities. In recent years, significant progress has been made in developing efficient synthetic methodologies and structurally diverse chalcone derivatives with improved pharmacological properties. Although several reviews have addressed individual aspects of chalcone chemistry, an integrated evaluation of recent advances in synthesis, biological activity, structure-activity relationships, and emerging drug-discovery strategies remains valuable. This review provides a comprehensive overview of the recent advances in chalcone synthesis during the last decade, especially from 2016 to 2026, highlighting both classical approaches, including Claisen-Schmidt condensation, and modern synthetic strategies based on transition metal-catalyzed coupling reactions, green chemistry, one-pot protocols, microwave-assisted synthesis, and other alternative methodologies. The role of chalcones as valuable intermediates for the synthesis of biologically important heterocyclic compounds is also discussed.In addition to synthetic developments, recent progress in the biological applications of chalcone derivatives is critically summarized. Representative studies describing anticancer, antibacterial, anti-inflammatory, and antioxidant activities are reviewed, with particular emphasis on the relationship between chemical structure and biological performance. The effects of structural modification, heterocyclic hybridization, substituent pattern, and advanced drug-delivery systems on biological activity are analyzed to identify key structure-activity relationship (SAR) trends that can guide the rational design of more potent chalcone-based molecules.Overall, the available evidence demonstrates that rational structural optimization has significantly expanded the therapeutic potential of chalcone derivatives. Although many promising compounds have shown remarkable biological activity, further investigations, particularly in vivo studies and clinical evaluation, remain necessary to facilitate their translation into therapeutic applications This review provides an updated perspective on chalcone chemistry and highlights future opportunities for the development of chalcone-based compounds as multifunctional therapeutic agents.