Antitumor potential of flavonoids derived from northeastern brazilian plants: preliminary studies on structure-cytotoxic activity relationship / Potencial antitumoral de flavonóides isolados de plantas do nordeste brasileiro: estudos preliminares da relação estrutura-atividade citotóxica
AUTOR(ES)
Gardênia Carmen Gadelha Militão
DATA DE PUBLICAÇÃO
2005
RESUMO
In searching for anticancer compounds derived from plant sources, 18 flavonoids were assayed for their cytotoxic potentials and the results were compared for structure-activity relationship purposes. The flavonoid group was subdivided in flavones and pterocarpans. The cytotoxic activity was initially evaluated on tumor cell lines, through the MTT assay, and on sea urchin eggs development. The pterocarpans showed a consistently higher activity on both assays. For the flavones, some structure-activity observations can be highlighted: a) a hydroxyl instead of a methoxyl group on C4 and C5 positions increases activity; b) a hydroxyl and a sugar on C3 position decreases activity and, by the data acquired, it can be emphasized that the methoxyl on C3 increases activity and c) the methoxyl on C7 position increases activity. The pterocarpans, a methoxyl group on C2 position increases the cytotoxic activity. Since the 2,3,9- trimethoxypterocarpan showed the best results in both assays, mode of action studies were conducted for the non-prenylated pterocarpans as an attempt to understand the influence of these groups over their bioactivity. All pterocarpans tested reduced cell viability, as indicated by the trypan blue assay, except for the 3,10-dihydroxy-9-methoxypterocarpan at 12,5 micrograma/mL. They also inhibited DNA synthesis and 2,3,9-trimethoxypterocarpan induced morphological cell alterations, which could be suggestive of apoptosis. On the assays for induction of cellular apoptosis this same compound caused DNA fragmentation and mitochondria depolarization, therefore maintaining membrane integrity, typical apoptotic signs. The other compounds, besides DNA fragmentation, there was noticeable loss of membrane integrity on higher concentrations, an indicative cell death by necrosis. Based on these observations, it is conclusive that the methoxyl group on C2 position is an important pharmacophoric unit for pterocarpans, which emerge as a potential class of anticancer chemicals.
ASSUNTO(S)
ensaios de seleção de medicamentos antitumorais pterocarpanos flavonoids pterocarpans antineoplásicos fitogênicos pharmacology drug screening assays, antitumor farmacologia flavonóides rubiaceae doxorrubicina taxóides farmacologia fitoterapia paclitaxel camptotheca fabaceae asteraceae podofilotoxina
ACESSO AO ARTIGO
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=100Documentos Relacionados
- Potencial antitumoral de substâncias isoladas de plantas do Cerrado brasileiro: estudos preliminares do mecanismo de ação da atividade citotóxica
- Propriedades químico-quânticas empregadas em estudos das relações estrutura-atividade
- Efeito de flavonoides na fosfoproteina tirosina fosfatase : mecanismos cineticos e relações estrutura-atividade
- Estudos de relações estrutura-atividade quantitativas (QSAR) de bis-benzamidinas com atividade antifúngica
- Estudo estrutura-atividade do taxol e derivados