3D-QSAR studies of pyruvate dehydrogenase kinase inhibitors based on a divide and conquer strategy

Abstract

PDHK is a highly specific enzyme, which inhibits PDC thereby reducing the conversion of pyruvate to AcetylCoA leading to increased glucose and lactate level contributing to various pathological disease states. 3D-QSAR CoMFA studies were performed on diverse PDHK inhibitors based on maximum common substructural alignments of different classes of molecules with the selected reference molecule using a divide and conquer strategy. Statistically robust CoMFA model was obtained with a cross-validated correlation coefficient of 0.561 and conventional correlation coefficient of 0.990. Predictive correlation coefficient r2pred was found to be 0.875. CoMFA study of pyruvate dehydrogenase kinase inhibitors based on a divide and conquer approach for alignment is reported.