ABSTRACT
Herein, we describe a new approach towards the synthesis of selenosemicarbazones. The reaction involves an O-Se exchange of semicarbazones using Ishihara reagent. Eleven selenosemicarbazones were prepared using this methodology, with low to moderate yields. Among the prepared compounds the m-bromo phenyl methyl derivative 1b was selected to be evaluated in vivo, in a murine model of acute Chagas' disease. Compound 1b 10 mg/kg bw/day reduced 50% of parasitaemia profile compared with the control group, but was less effective than Benznidazole (50 mg/kg bw/day reduced 90%) and toxic. These studies are important to guide future Chagas drug design.
Subject(s)
Chagas Disease/drug therapy , Organoselenium Compounds/chemical synthesis , Organoselenium Compounds/therapeutic use , Semicarbazones/chemical synthesis , Semicarbazones/therapeutic use , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/therapeutic use , Acute Disease , Animals , Chemistry Techniques, Synthetic , Drug Design , Male , Mice , Mice, Inbred BALB C , Organoselenium Compounds/chemistry , Semicarbazones/chemistry , Trypanocidal Agents/chemistry , Trypanosoma cruzi/drug effectsABSTRACT
La tripanosomiasis americana y la leishmaniosis son problemas de salud pública relevantes en Iberoamérica. Se evaluó la actividad antiparasitaria in vitro de extractos de cortezas y hojas de Erythrina crista-galli L., E. dominguezii Hassl y E. falcata Benth sobre formas tripomastigotas de Trypanosoma cruzi y promastigotas de Leishmania amazonensis, L. infantum L. braziliensis. El extracto de corteza de E. dominguezii Hassl presentó CI50 de 11,7 µg/ml y 14,9 µg/ml con dos cepas de T. cruzi, Ypsilon y Cl Brener. El extracto de hoja presentó CI50 mayor a 250 µg/ml. La corteza de E. falcata Benth tuvo CI50 de 11,29 µg/ml y 7,37 µg/ml con Ypsilon y Cl Brener y el extracto de hojas CI50 de 37,2 µg/ml y 25,68 µg/ml. El extracto de hojas de E. crista-galli L. presentó CI50 mayor a 250 µg/ml, y el de corteza CI50 11,2µg/ml y 7,1µg/ml con Ypsilon y Cl Brener. El extracto de corteza de E. dominguezii Hassl presentó CI50 de 3,22 µg/ml, 6,94 µg/ml y 1,9 µg/ml para L. amazonensis, L. infantum y L. braziliensis y en hojas la CI50 fue mayor a 100 µg/ml. La corteza de E. crista-galli L. tuvo CI50 de 2,1 µg/ml, 2,09 µg/ml y 1,6 µg/ml para las tres especies. El extracto de hoja tuvo una CI50 mayor a 100 µg/ml. El extracto de corteza de E. falcata Benth tuvo CI50 de 2,17 µg/ml, 2,09 µg/ml y 1,52 µg/ml con las tres especies de Leishmania y el de hoja CI50 de 14,9 µg/ml, 10,4 µg/ml y 11,6 µg/ml. Los extractos de corteza podrían ser una alternativa para el tratamiento de estas enfermedades parasitarias, previa confirmación con estudios in vivo y toxicidad
Subject(s)
Leishmania braziliensis , Leishmania infantum , Trypanosoma cruziABSTRACT
Chagas disease is becoming a public health problem in Latin America due to the wide distribution, the high prevalence, the magnitude of the damage caused and the difficulties to control it. In Paraguay, the disease is mainly distributed in the departments of Paraguari, Cordillera and Central. Prevalence in marginal zones, where migrations from rural populations and endemic areas make possible the urbanization of the disease, has no been studied yet. This is a descriptive study with a cross-sectional sampling and a probabilistic system recruitment carrred out in school aged children from marginal zones of Asuncion to determine the prevalence of Chagas' disease. Serological methods, parasite isolation and questionnaires were used to achieve the goals. Nine hundred and fifty three children were studied to determine the prevalence of Chagas' disease in marginal zones which was 1.4 percent
