Evaluation of the mutagenic potential and in vitro metabolization of three anti-inflammatory parsalmide analogues / Avaliação do potencial mutagenico e metabolização in vitro de tres analogos do antiinflamatorio parsalmide

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

In this study, the mutagenicity of the anti-inflammatory parsaJmide [5-amino-N-butyl-2-(2-propynyloxy)-benzamide] analogues PA7 [5-anuno-N-butyl-2-cyclohexyloxy-benzamide], PA10 [5-amino-N-butyl-2-phenoxy-benzamide] and PA31 [5-arnino-N-butyl-2-(p-tolyloxy)-benzamide] was determined by an Ames Salmonella assay. The experiments were performed by preincubating the compounds in the absence and presence of a post-mitochondrial fraction (S9) of rat liver homogenate from phenobarbital/p-naphtoflavone treated rats. No mutagenic effect was observed after direct testing (no S9 added) in Salmonella typhymurium&strains TA98, TA100, TA102, TA1535 and TA1537. However, in the presence of S9, the test substances triggered mutagenic responses in strains TA100 and TA98. PA31 presented the strongest mutagenic potential. The reversion rates in the presence of PA31 were about 2-19 folds higher than spontaneous mutation rates. In the presence of PA7, the reversion increased 2-14 folds over spontaneous rates. While PA10 showed a relatively mild mutagenic potential, as the number of revertants did not exceed 2.5 times the number of spontaneous mutations. Mass spectrometric analysis of the in vitro biotransformation showed that S9 converted (%), regioselectively, PA7 (19%), PA10 (7%) and PA31 (12%) into hydroxy-derivatives.

ASSUNTO(S)

mutagenese anti-inflammatory agents agentes antiinflamatorios mutagenesis

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