P56(lck) kinase inhibitor studies: a 3D QSAR approach towards designing new drugs from flavonoid derivatives.

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on 3D-QSAR (3D-quantitative structure activity relationship) studies were carried out on 97 flavonoid derivatives as potent P56(lck) protein tyrosine kinase inhibitors. The best prediction was obtained with CoMFA standard model (q² = 0.838, r² = 0.948) using steric, electrostatic along with CoMSIA standard model (q² = 0.714, r² = 0.921) using steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. Of the 97 molecules a training set of 76 compounds and the predictive ability of the QSAR model were assessed employing a test set of 21 compounds. The resulting CoMFA and CoMSIA contour maps were used to identify the structural features relevant to the biological activity in this series of flavonoid derivatives, based upon which we identified and designed 10 novel molecules that showed superior inhibitory activity against P56(lck) protein which shed new light on effective therapeutic agents against these classes of enzymes.