Combined 3D-QSAR Modeling and Molecular Docking Studies on Pyrrole-Indolin-2-ones as Aurora A Kinase Inhibitors

International Journal of Molecular Sciences

Yong Ai²  Shao-Teng Wang²  Ping-Hua Sun¹ 

[1] Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China; E-Mail:;College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China; E-Mails:

关键词: 3D-QSAR;    CoMFA;    CoMSIA;    Docking;    pyrrole-indoline-2-ones;    Aurora kinases;   

DOI  :  10.3390/ijms12031605

来源: mdpi

【 摘 要 】

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 r²_cv values of 0.726 and 0.566, and r² 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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.