Molecular docking analysis of PPARγ antagonists for obesity associated diabetes management

Obesity is a major metabolic disorder in developed countries, with an increasing number of people affected globally. PPARγ is primarily expressed in adipose tissue with a lesser extent in other tissues. PPARγ is an important mediator in several metabolic processes such as insulin sensitivity and adipogenesis. Because of its critical role in these processes, PPARγ is regarded as a critical target for therapeutic intervention in obesity treatment. A library of 2,320 bioactive compounds was screened insilico to identify compounds that strongly interact with the PPARγ protein. The compounds Z1982689600, Z2235802137, Z2235801970, and Z2037275165, demonstrated notable binding affinity values towards the PPARγ protein with values of -12.1, -11.7, -11.4, and -11.4 kcal/mol, respectively, which were higher than the binding affinity value observed for the control compound (-10.5 kcal/mol). These compounds bind tightly to PPARγ and have several amino acid residue interactions in common with the control compound. In addition, these compounds meet the ADMET criteria. These compounds could aid in the development of PPARγ antagonists for the management of obesity associated diabetes. However, additional research is needed to optimize their efficacy in wet laboratory conditions.