Thiazolidinedione nucleus: a molecular beacon in treatment of diabetes

T2D (Type 2 Diabetes) is a chronic metabolic disorder characterized by insulin resistance and persistent hyperglycemia. Thiazolidinediones (TZDs), an important class of anti-diabetic agents, act by improving insulin sensitivity resulting in increased activity of the peroxisome proliferator-activated receptor gamma (PPARγ). However, clinical adoption of TZDs is tempered by the fear of side effects including weight gain, fluid retention, and, rarer but more severe, heart failure or acute bladder cancer. A review is made of the evolving therapeutic potential of the TZD scaffold beyond its conventional use in T2DM management. The versatile TZD moiety has been used for functional group modification to diverse functional groups and has also been looked into as promising therapeutic applications. The advances in TZD research have been reviewed comprehensively in this paper with particular emphasis on TZD molecular mechanisms, SAR and potential application in type 2 diabetes. The pharmacokinetic and pharmacodynamic strategies used to optimize the profiles of TZD derivatives are discussed, as well as adverse effects and drug–drug interactions. This review brings together the latest findings to illuminate the broad spectrum potential of TZDs, and to provide motivation for future efforts to exploit this chemical framework for therapeutic applications of its own.