P56lck kinase inhibitor studies: a 3D QSAR approach towards designing new drugs from flavonoid derivatives. (1st January 2014)

• Record Type: Journal Article
• Authors: Gunda, Shravan Kumar; Mulukala Narasimha, Sandeep Kumar; Shaik, Mahmood
• Is Part Of: International journal of computational biology and drug design. Volume 7:Number 2/3(2014)
• Page Start: 278
• Page End: 294
• Publication Date: 2014-01-01
• Subjects: P56lck -- protein tyrosine kinase (PTK) inhibitors -- comparative molecular field analysis -- CoMFA -- comparative molecular similarity indices analysis -- CoMSIA -- molecular docking -- drug designing -- 3D-QSAR studies -- contour maps -- partial least squares -- PLS -- novel drugs; Computational biology -- Periodicals; Drugs -- Design -- Periodicals; 570.285
• Languages: English
• ISSNs: 1756-0756

Abstract

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 ( q 2 = 0.838, r 2 = 0.948) using steric, electrostatic along with CoMSIA standard model ( q 2 = 0.714, r 2 = 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.