Novel nitroimidazoles with trypanocidal and cell growth inhibition activities.
Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 18 million people in Latin America and is an important cause of heart disease. Although transmission has been reduced, an effective therapy for the infected population is lacking. New nitroimidazoles were designed and synthesized aimed at the development of a trypanocidal drug. The coupling of nitroimidazoles with heterocyclic N-trifluoromethyltriazolyl and pyrazolyl groups, 5-[N-(3-(5-trifluoromethyl)-1H-1,2,4-triazolyl)]amino-1-methyl-4-nitroimidazole (compound 4) and 5-N-(1-pyrazolyl)-1-methyl-4-nitroimidazole (compound 5). The in vitro trypanocidal effects of compounds 4 and 5 were evaluated. The results demonstrated that compound 5 was the most active compound, killing about 100% and 64% of the parasites in 0.3 mg/ml and 0.003 mg/ml concentrations, respectively. Interestingly, compound 4 also inhibited myeloma cell growth in a dose-dependent manner.
Boechat
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N
Department of Research and Development, Far-Manguinhos, Fundação Oswaldo Cruz, R. Sizenando Nabuco, Rio de Janeiro, Brazil.
Carvalho
A S
AS
Fernandez-Ferreira
E
E
Soares
R O
RO
Souza
A S
AS
Gibaldi
D
D
Bozza
M
M
Pinto
A C
AC
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000469:parasitology; D009101:Multiple Myeloma; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D012756:Sheep; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development; D014407:Tumor Cells, Cultured
C438210:5-(N-(3-(5-trifluoromethyl)-1H-1,2,4-triazolyl))amino-1-methyl-4-nitroimidazole; C438209:5-N-(1-pyrazolyl)-1-methyl-4-nitroimidazole; D009593:Nitroimidazoles; D014344:Trypanocidal Agents