Development of Heterocyclic PPAR Ligands for Potential Therapeutic Applications

Abstract

The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure–activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

New Insights into the Role of PPARγ in Skin Physiopathology

“…Typically, PPARs are activated by binding specific ligands that can be natural or synthetic compounds. Fatty acids and their derivatives are examples of endogenous ligands, while synthetic ligands include therapeutic drugs such as thiazolidinediones (TZDs) (PPARγ agonists) and fibrates (PPARα agonists) [ 2 , 6 , 35 , 36 ]. In particular, TZDs, such as pioglitazone, and WY14643 are some of the receptor ligands that have demonstrated promise in the management of a range of skin conditions, including psoriasis, atopic dermatitis, and skin cancers [ 20 , 28 , 37 , 38 ].…”