RESUMO
The cytotoxicity of 18 new 1,2,6-thiadiazin-3,5-dione 1,1-dioxides was evaluated. This group of products was previously assayed against epimastigotes of Trypanosoma cruzi and some of them showed a high antiprotozoal activity. Thereafter 13 compounds with a high anti-epimastigote activity and low cytotoxicity were selected to be assayed against amastigotes. Some of the products showed the same or even lower cytotoxicity than nifurtimox and benznidazole, but most of them were very toxic for macrophages at 100 microg/ml. Only one of the compounds had an anti-amastigote activity similar to that of reference drugs at 10 microg/ml, but unfortunately this disappeared at lower concentrations.
Assuntos
Antiprotozoários/farmacologia , Tiadiazinas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Testes de Sensibilidade ParasitáriaRESUMO
In a search for antichagasic drugs, 14 new 4-(nitroarylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide derivatives were synthesized and tested in vitro against the epimastigote form of Trypanosoma cruzi and some of them showed important antiprotozoan activity. Attempts to synthesize new 4-(nitroarylidene)-3,5-diamino-1,2,6-thiadiazine 1,1-dioxides were unsuccessful. The antichagasic properties of nitroarylidene-malononitrile and nitroarylidene-cyanoacetamide derivatives, thus obtained, were also tested. The cytotoxic properties against Vero cells of compounds which showed remarkable in vitro antichagasic activity were evaluated. All compounds tested exhibited high toxicity percentages at 100 micrograms/ml. However, compound 3c showed in vitro antichagasic and cytotoxic properties such as nifurtimox at the dose of 10 micrograms/ml.
Assuntos
Tiadiazinas/síntese química , Tripanossomicidas/síntese química , Animais , Chlorocebus aethiops , Humanos , Espectroscopia de Ressonância Magnética , Nifurtimox/química , Nifurtimox/farmacologia , Nifurtimox/toxicidade , Nitroimidazóis/química , Nitroimidazóis/farmacologia , Nitroimidazóis/toxicidade , Espectrofotometria Infravermelho , Tiadiazinas/farmacologia , Tiadiazinas/toxicidade , Tripanossomicidas/farmacologia , Tripanossomicidas/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Células VeroRESUMO
In a search for antiprotozoan compounds, 34 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives were synthesized and tested in vitro against Trypanosoma cruzi and Trichomonas vaginalis. Some of them showed important antiprotozoan activity. In vivo assays of compounds which showed remarkable in vitro activity against T. vaginalis were carried out.
