Avaliação "in vitro" e "in vivo" da atividade biologica dos derivados da n-aminometilftalimida sobre Trypanosoma cruzi

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

The search for new compounds capable to kill Trypanosoma cruzi, the etiologic agent of Chagas disease, been an interesting subject for researches. According to the literature, phthalimide compounds have showed good results against this parasite. The present study was carried out to estimate tripanocidal activity of seven N aminometylphthalimide compounds in two T. cruzi strains, with distinct characteristics, by "in vitro" and "in vivo" assays. The influence of these compounds for nitric oxide (NO) production by macrophages was also analyzed. The "in vitro" assay, were performed in two parsites stages: trypomastigotes and epimastiogotes stages. This assay demonstrated better activity of the N-( 4 metoxyfenyl)aminometylphthalimide (3) against trypomastigote stages of "Y" strain, in contrast to the N-(4-nitrofenyl)aminometylphthalimide (4) which promoted a better activity against T. cruzi Bolívia strain. However, N-(fenyl)aminometylphthalimide (1); N-( 4 metoxyfenyl)aminometylphthalimide (3); N-(4-nitrofenyl)aminometylphthalimide (4) and N-(4-benzenosulfonylguanidyl)aminometylphthalimide (5) showed greater activities against epimastigotes of "Y" strain. In contrast, N-(fenyl)aminometylphthalimide (1); N (4-metoxyfenyl)aminometylphthalimide (3); N-( 4-nitrofenyl)aminometylphthalimide (4) and N-( 4-benzenosulfonyl guanidyl)aminometylphthalimide (5); N-[ 4-benzenosulfonyl-(2 tiazolyl)amino] amino metylphthalimide (6) and N-[ 4-benzenosulfonyl-(2 pirimidyl)amino] aminometyl phthalimide (7), showed greater activities against Bolivia strain. The "in vivo" assays used as criteria parasitaemia, tissue parasitism and nuc1eus morphometric analyses of different tissues. Overall the compound N-[ 4-benzenosulfonyl (2-pirimidyl) amino] aminometylphthalimide (7) showed better activity against the "Y" strain whereas N -( fenyl)aminometylphthalimide (1); N-(4 metilfenyl)aminometylphthalimide (2) and N-( 4-metoxyfenyl)aminometylphthalimide (3) revealed a better activity against the "Bolivia" strain. The importance of Nitric Oxide (NO) production in controlling the acute infection of T. cruzi is well known. The influence of different compounds were analized by adding them in cytokine stimulated macrophage cultures and incubated for 24 hours. N aminometylphthalimide compounds showed a significant induction of NO production when comparing with those stimulated by INFy and LPS

ASSUNTO(S)

cultura histologia tripanossoma cruzi oxido nitrico

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