title: QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine kinase inhibitors.
abstract: The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.
authors.affiliation: a College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao , P.R. China and.
authors.forename: Cong-Min
authors.initials: CM
authors.lastname: Kang
authors.affiliation: a College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao , P.R. China and.
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Liu
authors.affiliation: a College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao , P.R. China and.
authors.forename: Xu-Hao
authors.initials: XH
authors.lastname: Zhao
authors.affiliation: a College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao , P.R. China and.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Dai
authors.affiliation: b Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology , Shanghai , P.R. China.
authors.forename: Jia-Gao
authors.initials: JG
authors.lastname: Cheng
authors.affiliation: a College of Chemical Engineering, Qingdao University of Science and Technology , Qingdao , P.R. China and.
authors.forename: Ying-Tao
authors.initials: YT
authors.lastname: Lv
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D062105:Molecular Docking Simulation; D000078183:Oxindoles; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D000078183:Oxindoles; D047428:Protein Kinase Inhibitors; C022960:2-oxindole; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: 3D-QSAR; CoMFA; CoMSIA; VEGFR-2 tyrosine kinase inhibitors; molecular docking