Research Projects

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder that accounts for over 90% of all diabetes cases. The disease is characterized by either insufficient insulin production or abnormal cell response to insulin. A combination of insulin sensitizers and secretagogues has become crucial in clinical diabetes therapy to control elevated blood glucose levels. The discovery of twelve Dipeptidyl Peptase IV (DPP IV) inhibitors (Gliptins) in the last two decades has changed the treatment strategy for hyperglycemic patients, acting as insulin secretagogue and improving glycated hemoglobin levels. Protein Tyrosine Phosphatase 1B (PTP 1B) inhibitors, insulin sensitizers, improve the insulin signaling cascade in patients with both diabetes and obesity. A dual inhibitory strategy targeting both DPP IV and PTP 1B inhibitors (DDPIs) is considered a legitimate approach to normalize blood glucose levels via a dual mechanism. This approach may provide significant pharmaceutical and development advantages, including cost-effectiveness, improved administration, and safety. The proposal proposes designing, synthesizing, and pharmacologically screening novel Dual inhibitors of DPP IV and PTP 1B for T2DM management. A virtual screening protocol will be used to identify lead molecules binding selectively with the active sites of both protein structures. A synthetic scheme will be developed for in silico designed and ADME optimized DDPIs, which will be screened against DPP IV and PTP 1B to assess their in vitro potency. The most potent molecules identified through in vitro assays will be selected for further anti-diabetic activity and safety assessment in animal models of T2DM.