title: Combined 3D-QSAR modeling and molecular docking studies on pyrrole-indolin-2-ones as Aurora A kinase inhibitors.
abstract: Aurora kinases have emerged as attractive targets for the design of anticancer drugs. 3D-QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)) and Surflex-docking studies were performed on a series of pyrrole-indoline-2-ones as Aurora A inhibitors. The CoMFA and CoMSIA models using 25 inhibitors in the training set gave r(2) (cv) values of 0.726 and 0.566, and r(2) values of 0.972 and 0.984, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the sulfo group, secondary amine group on indolin-2-one, and carbonyl of 6,7-dihydro-1H-indol-4(5H)-one groups were significant for binding to the receptor, and some essential features were also identified. Based on the 3D-QSAR and docking results, a set of new molecules with high predicted activities were designed.
authors.affiliation: College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China; E-Mails: aiyong0508@126.com (Y.A.); wst418638862@sohu.com (S.-T.W.).
authors.forename: Yong
authors.initials: Y
authors.lastname: Ai
authors.forename: Shao-Teng
authors.initials: ST
authors.lastname: Wang
authors.forename: Ping-Hua
authors.initials: PH
authors.lastname: Sun
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Song
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C456900:indolin-2-one; D064096:Aurora Kinase A