Asunto(s)
Aminopeptidasas/antagonistas & inhibidores , Encephalitozoon cuniculi/efectos de los fármacos , Encefalitozoonosis/tratamiento farmacológico , Encefalitozoonosis/mortalidad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Leucina/análogos & derivados , Péptidos , Animales , Antibacterianos/farmacología , Ciclohexanos , Modelos Animales de Enfermedad , Encephalitozoon cuniculi/crecimiento & desarrollo , Encefalitozoonosis/parasitología , Ácidos Grasos Insaturados/farmacología , Femenino , Leucina/farmacología , Leucina/uso terapéutico , Ratones , Ratones Desnudos , O-(Cloroacetilcarbamoil) Fumagilol , Pruebas de Sensibilidad Parasitaria/métodos , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéuticoRESUMEN
The activity of a series of compounds related to adenosine-N1-oxide (1) and 1-(benzyloxy)adenosine (42) against vaccinia virus has been determined both in vitro and in a vaccinia mouse tailpox model. Significant activities have been found both in vitro and in vivo for a number of the synthetic compounds.
Asunto(s)
Adenosina/análogos & derivados , Adenosina/síntesis química , Antivirales/síntesis química , Antivirales/farmacología , Óxidos N-Cíclicos/química , Virus Vaccinia/efectos de los fármacos , Vaccinia/tratamiento farmacológico , Adenosina/química , Adenosina/farmacología , Animales , Antivirales/química , Óxidos N-Cíclicos/farmacología , RatonesRESUMEN
Relatively few effective compounds are available for treating microsporidiosis in humans. In this study, several compounds were assayed for activity against Encephalitozoon intestinalis (Cali, Kotler et Orenstein, 1993) and Vittaforma corneae Shadduck, Meccoli, Davis et Font, 1990 in vitro. Of the benzimidazoles tested, albendazole was most effective and the MIC50 values were 8.0 ng/ml and 55.0 ng/ml for E. intestinalis and V. corneae, respectively. Fumagillin and its analogue, TNP-470 were nearly equally effective against both E. intestinalis and V. corneae. The MIC50 values of fumagillin were 0.52 ng/ml and 0.81 ng/ml, and the MIC50 values of TNP-470 were 0.35 ng/ml and 0.38 ng/ml for E. intestinalis and V. corneae, respectively. In addition, 12 of 44 purines and pteridines with putative tubulin binding activity that were synthesized at Southern Research Institute (SRI), inhibited microsporidial replication by more than 50% at concentrations that were not toxic to the host cells. Several chitin synthesis/assembly inhibitors inhibited growth of the microsporidia in vitro but were toxic for the host cells making it difficult to interpret the results. One exception was lufenuron, which caused no significant toxicity to the host cells and expressed approximate MIC50 values of 2.95 micrograms/ml and 6.3 micrograms/ml against E. intestinalis and V. corneae, respectively. These results warrant further studies on albendazole, fumagillin, TNP-470, lufenuron, and the selected SRI purines and pteridines for developing therapeutic strategies for microsporidiosis.
