Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.

Um estudo com microscopia eletrônica mostrou que a administração de dose única (500 mg/kg, p.o.) do composto 2-amino-5-(1-metil-5-nitro-2-imidazolil)-1 3, 4-tiadiazole induz, em camundongos inoculados com T. cruzi, lesões degenerativas das formas intracelulares do parasita. Alterações ultra estruturais são observadas 6 horas após a administração da droga e destruição ocorre em 18-36 horas. Tripomastigotas também desaparecem do sangue circulante dos animais 4-6 horas após o tratamento. O efeito em ambos os estágios evolutivos do T. cruzi é aparentemente responsável pelos efeitos in vivo desse derivado que é o mais ativo composto já testado em nosso laboratório na doença de Chagas.

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.