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Acta Physico-Chimica Sinica  2011, Vol. 27 Issue (05): 1214-1222    DOI: 10.3866/PKU.WHXB20110525
BIOPHYSICAL CHEMISTRY     
Target Identification of Isomalabaricane Terpenes Extracted from Sponges
TIAN Ran, LIU Zhen-Ming, JIN Hong-Wei, ZHANG Liang-Ren, LIN Wen-Han
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, P. R. China
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Abstract  

A strategy combining structure alignment and comparation, target cluster, and invert-docking screening were undertaken to detect the potential bioactivities of several isomalabaricane triterpenoids that were extracted from sponge. The prediction results revealed that the chemicals underwent myocardial ischemia treatment and had antineoplastic bioactivities. Enzymatic bioassays showed that epidermal growth factor receptor (EGFR), focal adhesion kinase (FAK), insulin-like growth factor 1 receptor (IGF1-R), c-Src kinase, and vascular endothelial growth factor receptor 2 (VEGF-R2) were potential targets for these compounds. They had IC50 values ranging from 0.41 g·m-3 (0.41 μg·mL-1) to 9.8 g·m-3 (9.8 μg·mL-1), which is meaningful for the use of these marine natural products as leads for further modifications to new agents. Ligand-target binding mode with these compounds were undertaken and indicated that the four studied chemicals bound well with the targets.



Key wordsMarine natural product      Isomalabaricane triterpenoid      Program of Prediction of Activity Spectra for Substances      Reverse virtual screening      Target identification      Antineoplastic bioactivity     
Received: 22 November 2010      Published: 13 April 2011
MSC2000:  O641  
Fund:  

The project was supported by the Major National Science and Technology Program-Key Drug Scheme Funds (2009ZX09501-002) and National Natural Science Foundation of China (20802006).

Corresponding Authors: LIU Zhen-Ming, LIN Wen-Han     E-mail: zmliu@bjmu.edu.cn; whlin@bjmu.edu.cn
Cite this article:

TIAN Ran, LIU Zhen-Ming, JIN Hong-Wei, ZHANG Liang-Ren, LIN Wen-Han. Target Identification of Isomalabaricane Terpenes Extracted from Sponges. Acta Physico-Chimica Sinica, 2011, 27(05): 1214-1222.

URL:

http://www.whxb.pku.edu.cn/Jwk_wk/wlhx/10.3866/PKU.WHXB20110525     OR     http://www.whxb.pku.edu.cn/Jwk_wk/wlhx/Y2011/V27/I05/1214

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