Insilico Proportional Molecular Docking Study and Analysis of Insulinotropic Activity of TZD Derivatives by PPARγ Activation

The thiazolidinediones (TZDs) have become one of the most commonly approved classes of medication for type 2 diabetes. In addition to glucose control, the TZDs have a number of pleiotropic effects risk factors for diabetes. Method: In the present studies, we investigate and assess the insulinotropic prospective using binding energy and pharmacological interaction of TZD derivatives using insilico proportional molecular docking relation approach against roziglitazone and to investigate the mechanism of action of TZD derivatives as a hypoglycemic agent, both in-vivo and in-vitro experiments were conducted. Investigations were conducted on the intestinal level by delaying or inhibiting glucose absorption, the peripheral level on insulin-sensitive tissues by facilitating the entry of glucose into cells such as muscle, and the pancreatic level by stimulating insulin secretion. Result: In this series, the most potent compounds were 6a and 6b having methoxy group at C5 position of TZD ring. Conclusion: 5-(substituted benzylidene)-2-(4-chloro-2-fluoro-5-methoxybenzylidene) hydrazono) thiazolidin-4-one have shown better antidiabetic activity. However, clinical trials with standardized extracts and uniform protocols have been with experimental animals and validated TZD derivatives clinical applicability as an antidiabetic agent. The outcomes of such studies may be useful for the clinical applications in humans and may open up a new therapeutic avenue.