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Int. J. Mol. Sci. 2011, 12(8), 5080-5097; doi:10.3390/ijms12085080
Article

Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors

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Received: 24 May 2011; in revised form: 1 August 2011 / Accepted: 2 August 2011 / Published: 10 August 2011
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Abstract: Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for embryonic blood vessel development and tumor angiogenesis. Several compounds that showed potent activity toward this attractive anticancer drug target in the assay have been reported. In order to investigate the structure-activity correlation of indolocarbazole series compounds and modify them to improve their selectivity and activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular docking was used to check the results. Based on the common sketch align, two good QSAR models with high predictabilities (CoMFA model: q2 = 0.823, r2 = 0.979; CoMSIA model: q2 = 0.804, r2 = 0.967) were obtained and the contour maps obtained from both models were applied to identify the influence on the biological activity. Molecular docking was then used to confirm the results. Combined with the molecular docking results, the detail binding mode between the ligands and Tie-2 was elucidated, which enabled us to interpret the structure-activity relationship. These satisfactory results not only offered help to comprehend the action mechanism of indolocarbazole series compounds, but also provide new information for the design of new potent inhibitors.
Keywords: Tie-2 kinase inhibitor; 3D-QSAR, CoMFA; CoMSIA; docking Tie-2 kinase inhibitor; 3D-QSAR, CoMFA; CoMSIA; docking
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.

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MDPI and ACS Style

Tian, Y.; Xu, J.; Li, Z.; Zhu, Z.; Zhang, J.; Wu, S. Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors. Int. J. Mol. Sci. 2011, 12, 5080-5097.

AMA Style

Tian Y, Xu J, Li Z, Zhu Z, Zhang J, Wu S. Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors. International Journal of Molecular Sciences. 2011; 12(8):5080-5097.

Chicago/Turabian Style

Tian, Yuanxin; Xu, Jian; Li, Zhonghuang; Zhu, Zhengguang; Zhang, Jiajie; Wu, Shuguang. 2011. "Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors." Int. J. Mol. Sci. 12, no. 8: 5080-5097.



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