RESUMEN
FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.
Asunto(s)
Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Depsipéptidos , Péptidos Cíclicos/uso terapéutico , Neumonía por Pneumocystis/tratamiento farmacológico , Animales , Antifúngicos/farmacología , Aspergilosis/mortalidad , Aspergillus fumigatus/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candidiasis/mortalidad , Modelos Animales de Enfermedad , Femenino , Hemólisis/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Ratones Desnudos , Pruebas de Sensibilidad Microbiana , Péptidos Cíclicos/farmacología , Pneumocystis/efectos de los fármacos , Neumonía por Pneumocystis/mortalidad , Resultado del TratamientoRESUMEN
The therapeutic effectiveness of water-soluble echinocandin compounds obtained from Coleophoma empetri F-11899, which has a strong inhibitory effect on the growth of fungi, was examined in nude mice with experimental Pneumocystis pneumonia. The studies demonstrated the potential usefulness of the compounds.