Antichagasicos 3-[4 -bromo-(1,1 -bifenil)-4-il]-3-(4-x-fenil)-N,N-dimetil-2-propen-1-amina

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

The present work describes the toxicological and pharmacological effects of two antichagasic compounds, diarylpropenamine derivatives, in rodents. The unsubstituted diarylpropenamine derivative, 3-[4 -bromo-(1,1 -biphenyl)- 4-iy]-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (where X = H), considered the prototype compound of this series, was chosen in order to study acute toxicity , lethal median dose (LD50), effects on the central nervous system and metabolism. Single dose of this compound produced general activity decrease, motor decoordination and muscle tone decrease, especially at doses of 125 and 140 mg.kg, its LD50 was 123 mg.kg. Detectable depressor or stimulant effects on the central nervous system were not observed in the open field test as well in the pentobarbital-induced sleeping time; also, anticonvulsivant activity was not observed in the pentiletetrazole-induced seizure model. Metabolism studies, carried out by high-performance liquid chromatography, revealed that fecal via seems to be the major route of excretion for unsubstituted derivative. In addition, no metabolite or conjugated form was detected in feces or urine samples. The therapeutic effects of bromo (where X = Br) and unsubstituted derivatives were assessed in mice infected with T. cruzi (Y strain). The first compound displayed a strong protective effect against the naturally death caused by the infection, combined with a remarkable decrease in the parasitemic levels. The second one, on the other hand, did not produce satisfactory effects under similar treatment conditions.

ASSUNTO(S)

toxidade chagas doença de

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