Ligand-based QSAR studies on the indolinones derivatives as inhibitors of the protein tyrosine kinase of fibroblast growth factor receptor by CoMFA and CoMSIA

Abstract

Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinones derivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) to FGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models were generated using CoMFA and CoMSIA with grid spacing 2 Å. After the PLS analysis the best predicted CoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out (LOO) cross validated value (r2cv) and non-cross validated conventional value (r2ncv) are 0.543 and 0.938, respectively.