Intriguing Thiazolidinediones as PPAR γ Agonists: A Review

Abstract

Diabetes mellitus is a chronic metabolic disorder marked by persistently elevated blood sugar levels. left untreatedover a long duration can cause multiple body disorders and may cause a person's early death. Though a traditional disorder, typeII diabetes prevalence is increasing daily, especially in the adolescent population worldwide. Peroxisome proliferator-activatedreceptor (PPAR) is a group of receptors consisting of three isoforms (PPAR α, PPAR β/δ, and PPAR γ. PPAR γ is involved inglucose metabolism by facilitating insulin's actions. Thiazolidinedione is a heterocyclic moiety standing pre-eminent in treatingdiabetes mellitus as a PPAR Gamma activator. Thiazolidinedione is a five-membered heterocyclic organic compound, athiazolidine derivative consisting of two carbonyl groups at positions 2 and 4 of the thiazolidine ring. Thiazolidinediones possessan idiosyncratic scaffold featuring a hydrogen bond acceptor region and hydrogen bond donating region at the third and fifthpositions. Thiazolidinedione is an indispensable pharmacophore with many pharmacological activities like antiproliferative,antiviral, antibacterial, tyrosine kinase inhibitory, aldose reductase inhibitory, alpha-glucosidase inhibitory, anti-inflammatory,antioxidant, antitubercular, antihyperlipidemic, etc. Many drugs have been introduced but later have been reticent because ofserious side effects like liver toxicity, CVS toxicity, etc. Pioglitazone and Rosiglitazone have been marketed medications fortreating type II diabetes. This review article deliberates all the cardinal points of thiazolidinediones as PPAR agonists in treatingdiabetes mellitus, which were precluded in some articles. We aim to have an all-embracing review of thiazolidinediones as PPARgamma agonists. The review's objective is to inspire researchers to develop a more superior, secure, and efficient anti-diabeticmedication by thoroughly understanding the molecular mechanisms of thiazolidinediones at the PPAR gamma receptors, theirrisks, and the effect of the various substitutions on the thiazolidinedione.