A Review of Natural and Synthetic Chalcones as Anticancer Agents Targeting Topoisomerase Enzymes
François‐Xavier Toublet, Aurélie Laurent, Christelle Pouget
Abstract
Cancer remains one of the leading causes of morbidity and mortality worldwide, driving the search for innovative and selective therapeutic agents. Topoisomerases I and II are essential enzymes involved in key cellular processes such as DNA replication and transcription. They have emerged as valuable anticancer targets; thus, many inhibitors of topoisomerases have been designed and some of them are considered to be major anticancer agents such as anthracyclines, etoposide or irinotecan. A great deal of attention is currently being paid to chalcones, a class of naturally occurring compounds, since they exhibit a wide range of biological activities, including anticancer properties. These compounds are characterized by an open-chain structure and an α,β-unsaturated carbonyl moiety that enables interaction with cellular targets. Recent studies aiming to design anti-topoisomerase agents have identified both natural and synthetic chalcones, including chalcone-based hybrids. This review highlights the structural diversity of chalcones as topoisomerase inhibitors and particular attention is given to structure-activity relationship studies and molecular hybridization strategies aimed at optimizing the pharmacological profile of chalcones. These findings underline the potential of chalcones as promising scaffolds in the design of next-generation anticancer agents.