Molecular Docking Studies of Novel Thiazolidinedionederivatives as PPARγ Modulators

Abstract

Thiazolidinediones (TZDs), a well-known target of peroxisome proliferated receptors (PPARγ), have been clinically used as antidiabetic agents. PPARs belong to the nuclear receptor superfamily and are important targets (PPARs) for drugs that treat various metabolic disorders such as diabetes. We present comparative research on the meta-para substitution of benzylidene derivatives of thiazolidine-2,4-diones to identify their potential as modulators of PPARγ. PPARs are key drug targets in treating a range of metabolic disorders. In our previous study, we described 4-hydroxy benzylidene derivatives of thiazolidine-2,4-diones that exhibited a reversed orientation in the active site of PPARγ. The established pharmacophore was also discussed concerning the reversed conformation of the TZD fitting. In current silico studies, a focus is placed on meta-para-substituted benzylidene derivatives to identify H-bonding interactions analogous to those observed in the acidic head of rosiglitazone. All designed compounds exhibited strong hydrogen bonding interactions and displayed superior interaction energies compared to their monohydroxy counterparts. The results of a predicted ADMET report indicated that all molecules exhibited favourable hERG I & II properties, suggesting excellent metabolic stability.