ANTI-CRYPTOCOCCAL PEPTIDES

摘要

Antifungals based on dolastatin 10 and four structural modifications thereof (herein "peptides") and methods of treating a host afflicted with a fungi-induced infection are herein described. In broth macrodilution assays, these peptides were fungicidal for ATCC strains and clinical isolates of Cryptococcus neoformans. Speficitity for C. neoformans was also demonstrated in the solid-phase disk diffusion assay, and fungicidal activity confirmed in killing kinetics experiments. Broth macrodilution minimum inhibitory and minimum fungicidal concentrations for the most potent modification ranged from 0.0975-1.56 mu g/ml, and 0.0975-6.24 mu g/ml, respectively. The minimum inhibitory concentrations were nearly identical in the presence of human serum, but increased with lowered pH. Suitable dosage forms for use of the novel antifungals are also described.