Chimie médicale

Docking Studies and Evaluation of Anthranilic Acid Based PPARδ Agonists for the Treatment of Metabolic Syndromes

Abstract

Meenu Beniwal, Viney Lather, Vikramjeet Judge, Neelam Jain and Amit Beniwal

Metabolic syndrome (MS) is defined by a cluster of interconnected factors that directlyincrease the risk of coronary heart disease (CHD), other forms of cardiovascularatherosclerotic diseases (CVD) and Type 2 diabetes mellitus (T2DM). Several studies have suggested important role of PPARδ in regulating lipid metabolism and energy homeostasis in muscle and fat. The present research work was undertaken to design and develop novel moieties derived from anthranilic acid scaffold as PPARδ agonists that can be developed further for the management of metabolic disorders. The molecules were designed using receptor based drug design approach, by utilizing the X-ray crystallographic information of PPARδ from PDB database. Based on the pharmacophoric requirements for PPARδ binding, the anthranilic acid nucleus was chosen for the design of newer analogs by substitution of amide linker and introduction of lipophilic groups on aromatic system by using sulphonamide group as a linker. Amongst the several synthesized anthranilic acid derivatives, 5-chloro-2- [3-(4-nitro-phenylsulfamoyl)-benzoyl amino]-benzoic acid showed highest antidiabetic activity. The experimental results were found to be in concordance with that of the in silico results. Overall, this research work revealed the potential of novel anthranilic acid based PPARδ agonists in the management of MS. Further, these molecules can serve as the starting point for the development of more potent lead molecules for MS.