Cytotoxic oxasqualenoids from the red alga Laurencia viridis

被引:43
作者
Cen-Pacheco, Francisco [1 ]
Villa-Pulgarin, Janny A. [2 ,3 ]
Mollinedo, Faustino [2 ]
Norte, Manuel [1 ]
Daranas, Antonio H. [1 ]
Fernandez, Jose J. [1 ]
机构
[1] Univ la Laguna, Inst Univ Bioorgan Antonio Gonzalez, Tenerife 38206, Spain
[2] Univ Salamanca, CSIC, Ctr Invest Canc, Inst Biol Mol & Celular Canc, E-37007 Salamanca, Spain
[3] Univ Salamanca, Ctr Hispano Luso Invest Agr CIALE, APOINTECH, E-37185 Salamanca, Spain
关键词
Oxasqualenoids; Marine polyether; Laurencia; Integrin inhibitor; COUPLING-CONSTANTS; APOPTOSIS; ANTAGONISTS; TARGETS;
D O I
10.1016/j.ejmech.2011.04.051
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Three new polyether squalene derivatives 15-dehydroxythyrsenol A (2), prethyrsenol A (3) and 13-hydroxyprethyrsenol A (4) have been isolated from the red alga Laurencia viridis. Their structures were determined through the interpretation of NMR spectroscopic data and chemical correlations. In addition, four semi-synthetic compounds modulating the solubility of the lead compound dehydrothyrsiferol (1) were prepared without loss of activity. The cytotoxicity of the new compounds exhibited low mu M activities. In order to explain their biological properties, docking simulations of the natural and synthetic compounds onto the alpha v beta 3 integrin binding region were carried out. (C) 2011 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:3302 / 3308
页数:7
相关论文
共 25 条
[1]   Marine natural products [J].
Blunt, John W. ;
Copp, Brent R. ;
Munro, Murray H. G. ;
Northcote, Peter T. ;
Prinsep, Michele R. .
NATURAL PRODUCT REPORTS, 2011, 28 (02) :196-268
[2]   INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS [J].
BROOKS, PC ;
MONTGOMERY, AMP ;
ROSENFELD, M ;
REISFELD, RA ;
HU, TH ;
KLIER, G ;
CHERESH, DA .
CELL, 1994, 79 (07) :1157-1164
[3]   Integrins as therapeutic targets: lessons and opportunities [J].
Cox, Dermot ;
Brennan, Marian ;
Moran, Niamh .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (10) :804-820
[4]   Impact of Natural Products on Developing New Anti-Cancer Agents [J].
Cragg, Gordon M. ;
Grothaus, Paul G. ;
Newman, David J. .
CHEMICAL REVIEWS, 2009, 109 (07) :3012-3043
[5]   DNA and non-DNA targets in the mechanism of action of the antitumor drug trabectedin [J].
David-Cordonnier, MH ;
Gajate, C ;
Olmea, O ;
Laine, W ;
de la Igiesia-Vicente, J ;
Perez, C ;
Cuevas, C ;
Otero, G ;
Manzanares, I ;
Bailly, C ;
Mollinedo, F .
CHEMISTRY & BIOLOGY, 2005, 12 (11) :1201-1210
[6]   Discovery of small molecule integrin αvβ3 antagonists as novel anticancer agents [J].
Dayam, Raveendra ;
Aiello, Francesca ;
Deng, Jinxia ;
Wu, Yun ;
Garofalo, Antonio ;
Chen, Xiaoyuan ;
Neamati, Nouri .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (15) :4526-4534
[7]   Marine natural products [J].
Faulkner, DJ .
NATURAL PRODUCT REPORTS, 2002, 19 (01) :1-48
[8]   Marine polyether triterpenes [J].
Fernández, JJ ;
Souto, ML ;
Norte, M .
NATURAL PRODUCT REPORTS, 2000, 17 (03) :235-246
[9]  
Gajate C, 2000, INT J CANCER, V86, P208, DOI 10.1002/(SICI)1097-0215(20000415)86:2<208::AID-IJC10>3.0.CO
[10]  
2-E