Thiazolidine-2,4-Dione: Bridging the Gap Between Synthesis, SAR, and Biological Activities, and Computational Predictions

INTRODUCTION: Thiazolidinedione is one of the most important classes in medicinal chemistry. Thiazolidine-2,4-dione (TZD) is a versatile scaffold, best known for its use in the development of anti-diabetic drugs such as pioglitazone and rosiglitazone. Beyond their well-established antidiabetic properties, TZDs exhibit a wide range of biological activities including anticancer, anti-inflammatory, antibacterial, and neuroprotective effects, making them potential candidates for various therapeutic applications. METHODOLOGY: This review focuses on the complete journey of TZD derivatives-from their synthetic design to their inclusion in commercialized pharmaceutical products. Structure-activity relationship (SAR) studies were analyzed to understand how modifications in the TZD core affect binding affinity, selectivity, and therapeutic efficacy. In addition, the review consolidates findings from biological evaluations and computational studies that provide deeper insights into the mechanism of action and pharmacological potential of TZD derivatives. CONCLUSION: This review highlights the significance of the TZD scaffold as a multifunctional pharmacophore in drug discovery. By integrating synthetic strategies, SAR analysis, and advanced computational tools, TZD derivatives continue to show great potential for the development of new therapeutic agents for various diseases. The combined understanding of chemistry and biological activities of TZDs paves the way for innovative research and future drug design.