Thiazolidin-4-ones exhibit a highly adaptable and privileged core structure, consisting of a five-membered heterocyclic ring with a sulfur atom and a cyclic amide bond. Recent research, especially in the last decade, has extensively explored the various biological activities of this scaffold, highlighting its potential therapeutic applications. Several key features, such as drug-likeness, compatibility for diversity-oriented synthesis, and sensitivity to the redox environment of tumors, make it a promising structure for the development of anticancer agents. The thiazolidine-2,4-dione and thiazolidine-4-one are two classical forms of this scaffold, with the former receiving more attention compared to the latter. However, the thiazolidine-4-one core is increasingly attracting research interest, as reflected in numerous studies published in recent years. This comprehensive review primarily focuses on the anticancer potential of thiazolidine-4-one derivatives, exploring the structural variety and substitution patterns of compounds that feature this nucleus. The review explores the various enzymatic targets involved in drug discovery, highlighting their selectivity for cancerous tissues over healthy cells, as well as the structure-activity relationships (SAR). Future research perspectives are also discussed, with an emphasis on advancing translational studies. Further studies on pharmacokinetics and metabolic stability are recommended to move toward potential lead candidates for clinical application.
