RESUMO
Imidazolidin-4-one derivatives of primaquine were synthesized as potential double prodrugs of the parent drug. The title compounds inhibit the development of the sporogonic cycle of Plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. The imidazolidin-4-ones are very stable, both in human plasma and in pH 7.4 buffer, indicating that they are active per se. Thus, imidazolidin-4-ones derived from 8-aminoquinolines represent a new entry in antimalarial structure-activity relationships.
Assuntos
Antimaláricos/síntese química , Imidazolidinas/síntese química , Primaquina/análogos & derivados , Primaquina/síntese química , Animais , Anopheles/parasitologia , Antimaláricos/química , Antimaláricos/farmacologia , Estabilidade de Medicamentos , Humanos , Imidazolidinas/farmacologia , Técnicas In Vitro , Malária/sangue , Malária/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/efeitos dos fármacos , Primaquina/farmacologia , Relação Estrutura-AtividadeRESUMO
Aspergillus fumigatus causes lethal invasive aspergillosis in cortisone-treated mice while immunized mice are protected. Kinetics of interferon (IFN)-gamma, tumor necrosis factor-alpha, interleukin (IL)-12p40, IL-4 and IL-10 expression were assessed by reverse transcription-PCR in the spleen and lungs of mice. After immunization, mice were protected from otherwise lethal infection, with concomitant high expression levels of IFN-gamma early in the lungs and later in the spleen. In the lethal infection model cortisone-treated infected mice presented high expression levels of IL-10 in the spleen and in the lungs. Immunocompetent mice were able to control the disease and presented earlier expression of IL-12p40 and IFN-gamma in lungs and spleen. These results confirm the importance of Th1 dependent immunity against invasive aspergillosis.