Int. J. Mol. Sci. 2011, 12(3), 1605-1624; doi:10.3390/ijms12031605
Article

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

Received: 26 January 2011; Accepted: 28 February 2011 / Published: 1 March 2011
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 r2cv 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.
Keywords: 3D-QSAR; CoMFA; CoMSIA; Docking; pyrrole-indoline-2-ones; Aurora kinases
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MDPI and ACS Style

Ai, Y.; Wang, S.-T.; Sun, P.-H.; Song, F.-J. Combined 3D-QSAR Modeling and Molecular Docking Studies on Pyrrole-Indolin-2-ones as Aurora A Kinase Inhibitors. Int. J. Mol. Sci. 2011, 12, 1605-1624.

AMA Style

Ai Y, Wang S-T, Sun P-H, Song F-J. Combined 3D-QSAR Modeling and Molecular Docking Studies on Pyrrole-Indolin-2-ones as Aurora A Kinase Inhibitors. International Journal of Molecular Sciences. 2011; 12(3):1605-1624.

Chicago/Turabian Style

Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun. 2011. "Combined 3D-QSAR Modeling and Molecular Docking Studies on Pyrrole-Indolin-2-ones as Aurora A Kinase Inhibitors." Int. J. Mol. Sci. 12, no. 3: 1605-1624.

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