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

Autor(es)

Bruder, Marjorie ^[1] ; Vendramini-Costa, Debora Barbosa ^{[1, 2, 3]} ; de Carvalho, Joao Ernesto ^{[2, 3]} ; Pilli, Ronaldo Aloise ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Quim, Dept Quim Organ, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, BR-13083970 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Div Farmacol & Toxicol, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr CP, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 21, n. 17, p. 5107-5117, SEP 1 2013.
• Citações Web of Science: 16

Resumo

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. (AU)

• Processo FAPESP: 10/06178-8 - Síntese e avaliação de atividade citotóxica de análogos de goniotalamina
• Beneficiário: Marjorie Christine Paule Bruder
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/51602-5 - Biologia química: novos alvos moleculares naturais e sintéticos contra o câncer, estudos estruturais, avaliação biológica e modo de ação
• Beneficiário: Ronaldo Aloise Pilli
• Modalidade de apoio: Auxílio à Pesquisa - Temático