Molecular Docking, In-Silico ADMET Study and Development of 1,6-Dihydropyrimidine Derivative as Protein Tyrosine Phosphatase Inhibitor: An Approach to Design and Develop Antidiabetic Agents

Background: 1,6-Dihydropyrimidine exerts notable pharmacological efficiency and emerged as integral backbones for treatment of type-II diabetes mellitus. To optimize the in vitro and In-silico study we carried out on substituted 1,6-Dihydropyrimidine. The objective of the present study is to evaluate the binding interaction of 1,6-Dihydropyrimidine compounds with Protein Tyrosine Phosphatase (PTP1B) enzyme and also check ADME/T properties of best scored compounds.

Methods: The In-silico study (docking) was carried out through target Protein Tyrosine Phosphatase (PTP1B) retrieved from protein data bank having PDB ID: 2QBS and the anti diabetic activity of the test compounds was tested against protein tyrosine phosphatase (PTP1B) enzyme by using Calbiochem ® PTP1B colorimetric assay kit.

Results and Conclusion: The results of molecular Docking revealed that, with respect to their free binding energy 6A, 3K, 1B and 2K compounds have the lowest binding energy compared to positive control. In-silico ADME/T predictions revealed that all best scored compounds had good absorption as well as solubility characteristics through substrate binding sites. After conducting the in vitro studies it was observed that compounds having -3NO2, 3,4-OCH3, 4-NO2 and 4-Cl substitution on phenyl ring in the basic moiety shows good anti diabetic activity The present computational approach provided valuable information on the binding process of 1,6-Dihydropyrimidine compounds to the binding site of PTP-1B. These compounds may serve as potential lead compound for developing new 1,6- Dihyropyrimidine as a promising anti diabetic agent.