Synthesis of methoxylated goniothalamin, aza-goniothalamin and gamma-pyrones and their in vitro evaluation against human cancer cells

Autor(es)

Barcelos, Rosimeire Coura ^[1] ; Pastre, Julio Cezar ^[1] ; Caixeta, Vanessa ^[1] ; Vendramini-Costa, Debora Barbosa ^{[2, 3]} ; de Carvalho, Joao Ernesto ^{[2, 3]} ; Pilli, Ronaldo Aloise ^{[1, 2]}

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, Programa Posgrad Biol Celular & Estrutural, 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. 20, n. 11, p. 3635-3651, JUN 1 2012.
• Citações Web of Science: 26

Resumo

The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the gamma-pyrones and the azagoniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated. Furthermore, it was more potent than doxorubicin against NCI-ADR/RES, OVCAR-03 and HT-29 while being less toxic to human keratinocytes (HaCat). The 3,5-dimethoxy analogue 90 and 2,4,5-trimethoxy analogue 92 also displayed promising antiproliferative activity when compared to goniothalamin ( 1). These results provide new elements for the design and synthesis of novel representatives of this family of natural compounds. (C) 2012 Elsevier Ltd. All rights reserved. (AU)

• 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
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/16990-1 - Síntese e avaliação da atividade citotóxica de gama-diidropironas: análogos de goniotalamina e de abyssinona II
• Beneficiário: Júlio Cezar Pastre
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado