ISSN 1000-6818CN 11-1892/O6CODEN WHXUEU
Acta Phys Chim Sin >> 2011,Vol.27>> Issue(05)>> 1214-1222     doi: 10.3866/PKU.WHXB20110525         中文摘要
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
Full text: PDF (10413KB) HTML Export: BibTeX | EndNote (RIS)

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.

Keywords: Marine natural product   Isomalabaricane triterpenoid   Program of Prediction of Activity Spectra for Substances   Reverse virtual screening   Target identification   Antineoplastic bioactivity  
Received: 2010-11-22 Accepted: 2011-02-17 Publication Date (Web): 2011-04-13
Corresponding Authors: LIU Zhen-Ming, LIN Wen-Han Email:;

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).

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[J]. Acta Phys. -Chim. Sin., 2011,27 (05): 1214-1222.    doi: 10.3866/PKU.WHXB20110525

(1) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2007, 70, 461.
(2) Newman, D. J.; Cragg, G. M. Future Med. Chem. 2009, 1, 1415.
(3) Simmons, T. L.; Andrianasolo, E.; McPhail, K. Mol. Cancer Ther. 2005, 4, 333.
(4) Takamatsu, S.; Hodges, T. W.; Rajbhandari, I. J. Nat .Prod. 2003, 66, 605.
(5) Paul, V. J.; Arthur, K. E.; Ritson-Williams, R. Biol. Bull. 2007, 213, 226.
(6) Nagle, D. G.; Zhou, Y. D. Phytochem. Rev. 2009, 8, 415.
(7) Villa, F. A.; Gerwick, L. Immunopharm Immunot. 2010, 32, 228.
(8) Molinski, T. F.; Dalisay, D. S.; Lievens, S. L.; Saludes, J. P. Nat. Rev. Drug Discov. 2009, 8, 69.
(9) Bugni, T. S.; Richards, B.; Bhoite, L.; Cimbora, D.; Harper, M. K.; Ireland, C. M. J. Nat. Prod. 2008, 71, 1095.
(10) Thakur, N. L.; Jain, R.; Natalio, F.; Hamer, B.; Thakur, A. N.; Müller, W. E. Biotechnol. Adv. 2008, 26, 233.
(11) Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 1.
(12) Nicolaou, K. C.; Vourloumis, D.; Winssinger, N. Angew Chem. Int. Edit. 2000, 39, 44.
(13) Yeung, K. S.; Paterson, I. Chem. Rev. 2005, 105, 4237.
(14) Morris, J. C.; Phillips, A. J. Nat. Prod. Rep. 2010, 27, 1186.
(15) Tang, S. A.; Deng, Z. W.; Li, J.; Fu, H. Z.; Pei, Y. H.; Zhang, S.; Lin, W. H. Chin. Chem. Lett. 2005, 16, 353.
(16) Lv, F.; Deng, Z. W.; Li, J.; Fu, H. Z.; van Soest, R. W. M.; Proksch, P.; Lin, W. H. J. Nat Prod. 2004, 67, 2033.
(17) Lagunin, A.; Stepanchikova, A.; Filimonov, D.; Poroikov, V. Bioinformatics 2000, 16, 747.
(18) Filimonov, D. A.; Poroikov, V. V. Bioactive Compound Design: Possibilities for Industrial Use, 1st ed.; BIOS Scientific Publishers, Oxford (UK) BIOS Scientific Publishers: Oxford, UK, 1996; pp 47-56.
(19) ChemOffice Ultra 2005 (; Cambridge Soft Inc.: Cambridge, MA, 2005.
(20) SYBYL6.91 (; Tripos Inc.: St, Louis, MO, 2006.
(21) Lagunin, A.; Filimonov, D. A.; Poroikov, V. V. Cur. Phar. Des. 2010, 16, 1703.
(22) Ewing, T. J. A.; Makino, S.; Skillman, A. G.; Kuntz, I. D. J. Comput. Aid. Mol. Des. 2001, 15, 411.
(23) Lape, M.; Elam, C.; Paula, S. Biophys. Chem. 2010, 50, 88.
(24) Cross, J. B.; Thompson, D. C.; Rai, B. K.; Baber, J. C.; Fan, K.Y.; Hu, Y.; Humblet, C. J. Chem. Inf. Model. 2009, 49, 1455.
(25) McGaughey, G. B.; Sheridan, R. P.; Bayly, C. I.; Culberson, J. C.; Kreatsoulas, C.; Lindsley, S.; Maiorov, V.; Truchon, J. F.; Cornell, W. D. J. Chem. Inf. Model. 2007, 47, 1504.
(26) DesJarlais, R. L.; Gibbs, A. C.; Mohan, V.; Jaeger, E. P. J. Med. Chem. 2005, 48, 962.
(27) Perola, E.; Walters, W. P.; Charifson, P. S. Proteins 2004, 56, 235.
(28) Goodsell, D. S.; Morris, G. M.; Olson, A. J. J. Mol. Recognit. 1996, 9, 1.
(29) Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. J. Comput. Chem. 1998, 19, 1639.

Copyright © 2006-2016 Editorial office of Acta Physico-Chimica Sinica
Address: College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P.R.China
Service Tel: +8610-62751724 Fax: +8610-62756388
^ Top