QSAR and Binding Mode of a Series of Combretastatin Analogues as Tubulin Inhibitors

Chem. J. Chinese Universities

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QSAR and Binding Mode of a Series of Combretastatin Analogues as Tubulin Inhibitors

TIAN Ran^1,2, JI Yu-Bin¹, LIU Zhen-Ming², JIN Hong-Wei², ZHANG Liang-Ren²*, LIN Wen-Han^1,2*

1. Research Center on Life Science and Environmental Science, Harbin University of Commerce, Harbin 150076, China;
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Received:2007-03-06 Revised:1900-01-01 Online:2007-11-10 Published:2007-11-10
Contact: ZHANG Liang-Ren

Abstract

Abstract: The quantitative structure-activity relationship(QSAR) of a series of combretastatin analogues with ring B modification was studied. The two dimensional structure-activity relationship was carried out by genetic function analysis(GFA) method. The results indicate that Apol, PMI-mag, Dipole-mag, Hbond donor, and RadOfGyration descriptors contributed significantly to the activities. Furthermore, a three dimensional structure-activity was performed via comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). An analyses of CoMFA and CoMSIA models resulted in a cross validated coeffieciency(q²) of 0.630 and 0.634 respectively, which showed a strong predictive ability. The contourmaps of CoMFA and CoMSIA provided smooth and interpretable explanation of the structure-activity relationship of the selected compounds. A molecular docking was used to analyze and validate the QSAR models. Those results provide a useful information to design novel tubulin inhibitors.

Key words: Combretastatin analogues, QSAR, Genetic function analysis, Comparative molecular field analysis, Comparative molecular similarity indices analysis

CLC Number:

O641
O621

TrendMD:

TIAN Ran^1,2, JI Yu-Bin¹, LIU Zhen-Ming², JIN Hong-Wei², ZHANG Liang-Ren²*, LIN Wen-Han^1,2*. QSAR and Binding Mode of a Series of Combretastatin Analogues as Tubulin Inhibitors[J]. Chem. J. Chinese Universities, doi: .

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QSAR and Binding Mode of a Series of Combretastatin Analogues as Tubulin Inhibitors

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