Specific Activities of Dolastatin 10 and Peptide Derivatives against Cryptococcus neoformans
AUTOR(ES)
Pettit, Robin K.
FONTE
American Society for Microbiology
RESUMO
The biosynthetic peptide dolastatin 10 is currently in phase I and II cancer clinical trials. We evaluated the antifungal spectrum of dolastatin 10 and four structural modifications. In broth macrodilution assays, the peptides were fungicidal for American Type Culture Collection strains and clinical isolates (including fluconazole-resistant strains) of Cryptococcus neoformans but no other yeasts or filamentous fungi examined. Specificity for C. neoformans was also demonstrated in the solid-phase disk diffusion assay, and fungicidal activity was confirmed in time-kill experiments. For a methyl ester modification, the MICs at which 50 and 90% of 19 clinical isolates were inhibited (MIC50 and MIC90, respectively) were 0.195 and 0.39 μg/ml, respectively. The MFC50 (50% minimum fungicidal concentration) for this peptide was 0.39 μg/ml, and the MFC90 was 0.78 μg/ml. MICs and MFCs were identical or lower in the presence of human serum but increased with lowered pH. These peptides should be pursued as potential chemotherapeutics for C. neoformans, a leading cause of infection and mortality in immunocompromised patients.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=105973Documentos Relacionados
- Mouse-human immunoglobulin G1 chimeric antibodies with activities against Cryptococcus neoformans.
- In Vitro Activities and Postantifungal Effects of the Potent Dolastatin 10 Derivative Auristatin PHE
- In Vitro Activities of Ravuconazole (BMS-207147) against 541 Clinical Isolates of Cryptococcus neoformans
- Interactions of Posaconazole and Flucytosine against Cryptococcus neoformans
- Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole against Cryptococcus neoformans in vitro.