Abstract
A series of lipopeptide compounds co-produced during the fermentation of pneumocandin A0 (L-671,329) and related semisynthetic compounds were evaluated in vivo against Pneumocystis carinii pneumonia and systemic candidiasis. In addition, they were tested in vitro against a panel of pathogenic Candida species and in a Candida membrane 1,3-beta-D-glucan synthesis assay. The results of these studies demonstrate that pneumocandin A0 and pneumocandin B0 (L-688,786) are the most potent compounds when considering both antipneumocystis and anticandida activity. Other compounds in the series are selectively more potent against P. carinii or Candida albicans suggesting a diverging structure-activity relationship. Evaluation of these compounds for their ability to inhibit C. albicans 1,3-beta-D-glucan synthesis in vitro demonstrates that they inhibit this process. A positive correlation between 1,3-beta-D-glucan synthesis inhibition and in vitro antifungal activity was also demonstrated for some of the pneumocandins.
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