Artículos de revistas
Design, synthesis and in vitro evaluation against human cancer cells of 5-methyl-5-styryl-2,5-dihydrofuran-2-ones, a new series of goniothalamin analogues
Registro en:
Bioorganic & Medicinal Chemistry. Pergamon-elsevier Science Ltd, v. 21, n. 17, n. 5107, n. 5117, 2013.
0968-0896
1464-3391
WOS:000323294600026
10.1016/j.bmc.2013.06.044
Autor
Bruder, M
Vendramini-Costa, DB
de Carvalho, JE
Pilli, RA
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The present work describes the preparation of a novel series of compounds based on the structure of goniothalamin (1), a natural styryl lactone with known cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 17 goniothalamin analogues displaying the 5-methyl-2,5-dihydrofuran-2-one motif were prepared, and their cytotoxicity evaluated. While the analogues bearing methoxy and/or hydroxy groups on the aromatic moiety usually were at least three times less potent than the lead compound (1), ortho and para-trifluoromethyl analogues 10 and 11 exhibited levels of cytotoxicity similar to goniothalamin (1) against most cancer cell lines evaluated. One could suggest that the electronic effect of the trifluoromethyl group activates the inhibitor's electrophilic site via reduction of the electron density of the alpha,beta-unsaturated ester oxygen atom. These results provide new information on the structure activity relationship of these alpha,beta-unsaturated styryl lactones, thereby further focusing the design of novel candidates. (C) 2013 Elsevier Ltd. All rights reserved. 21 17 5107 5117 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP [2010/06178-8, 2009/51602-5]