Citocidade de derivados de beta -enaminocetonas em celulas de mamiferos

AUTOR(ES)

Claudia de Lourdes Soraggi

DATA DE PUBLICAÇÃO

1997

RESUMO

Studies on structure-activity relationships are essential for the development of new pharmacological drugs. In this work we have investigated the cytotoxicity of new structurally related synthetic compounds, the y-aminoalcohols 2-pentanol-4 benzylamine (PBA), 2-pentanol-4-phenylamine (PPA) and the corresponding tetrahydro-I,3-oxazines, 2-pentanol-4benzyloxazine (PBO) and 2-pentanol-4-phenyloxazine (PPO). The biological relevance of y-aminoalcohols and derivatives is based on their wide pharmacological application. We have firstly analysed the cytotoxicity of standard compounds to cultured hamster cells (V79 line), the alcohols Butanol-1, Heptanol-land Allyl Alcohol, by measuring of different endpoints. The Growth Inhibition Assay was the most sensitive endpoint to evaluate alcohols cytotoxicity. For this reason it was been used for evaluation of the y-aminoalcohols PBA, PPA and the oxazines PBO,PPO, respectively. The relative potencies were compared by determining the midpoint cytotoxicity, or ID50 value (dose required to induce 50% inhibition) for each compound. According to this, it was obtained the following order: PPO>PBO>Heptanol-l>PBA>PP A>But-l>A. Alcohol We analysed further the activity of each synthetic compound upon DNA synthesis in V79 cells. The DNA synthesis rate was determined by measuring 3H-thymidine uptake in exposed cultures. The results showed that the oxazines PBO and PPO were potent inhibitors of DNA synthesis in V79 cells, while the yaminoalcohols PBA and PP A affected only slightly the rate of synthesis, in the same concentration range (0.5-5.0 mM). These results indicate that the antireplicative activity of these oxazines is probably related to molecular cyclization. Our data point to the possible use of the oxazines PBO and PPO as antineoplasic agents

ASSUNTO(S)

toxicidade - testes fibroblasto relação estrutura-atividade (bioquimica)

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