Review of Recent Advances in Thiazolidin-4-One Derivatives as Promising Antitubercular Agents (2021-Present).

Tuberculosis (TB) remains one of the leading causes of mortality worldwide, exacerbated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains. In the pursuit of novel therapeutic strategies, thiazolidin-4-one derivatives have gained significant attention due to their structural diversity and broad-spectrum biological activities. This review provides a comprehensive summary of recent advances (2021-present) in the synthesis, structure-activity relationship (SAR), and mechanisms of action of thiazolidin-4-one derivatives as promising antitubercular agents. A detailed discussion of synthetic pathways is presented, including classical and multi-component reactions leading to various subclasses such as thiazolidine-2,4-diones, rhodanines, and pseudothiohydantoins. The SAR analysis highlights key functional groups that enhance antimycobacterial activity, such as halogen substitutions and heterocyclic linkers, while molecular docking and in vitro studies elucidate interactions with key Mtb targets including InhA, MmpL3, and DNA gyrase. Several compounds demonstrate potent inhibitory effects with MIC values lower than or comparable to first-line TB drugs, alongside favorable cytotoxicity profiles. These findings underscore the potential of thiazolidin-4-one scaffolds as a valuable platform for the development of next-generation antitubercular therapeutics.