WF11899A, B and C, novel antifungal lipopeptides. II. Biological properties.
WF11899A, B and C, novel water-soluble lipopeptides related to the echinocandins, possess potent anti-Candida activities. The IC50s of the compounds against four clinical isolates of Candida albicans ranged from 0.004 to 0.03 microgram/ml by microbroth dilution assay. These compounds mildly suppressed the growth of Aspergillus fumigatus and A. niger. WF11899A, B and C showed a potent in vivo anti-Candida activity. Particularly, WF11899A was superior to cilofungin, and equal to fluconazole. 1,3-beta-glucan synthase was inhibited by these compounds at the IC50s of 0.7, 0.7 and 1.8 micrograms/ml for WF11899A, B and C, respectively. However, they hemolysed mouse red blood cells in vitro at the concentration of 62 micrograms/ml.
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
T
T
Iwamoto
A
A
Fujie
K
K
Nitta
S
S
Hashimoto
M
M
Okuhara
M
M
Kohsaka
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D001234:Aspergillus niger / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006461:Hemolysis; D055666:Lipopeptides; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000633:toxicity; D029702:Schizosaccharomyces pombe Proteins
D000935:Antifungal Agents; D055666:Lipopeptides; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D029702:Schizosaccharomyces pombe Proteins; C090474:WF 11899A; C090475:WF 11899B; C090476:WF 11899C; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase