FR209602 and related compounds, novel antifungal lipopeptides from coleophoma crateriformis no. 738. II. In vitro and in vivo antifungal activity.
The biological activities of the novel echinocandin-like lipopeptides, FR209602, FR209603 and FR209604, were evaluated. These compounds showed antifungal activity against Candida albicans and Aspergillus fumigatus attributed to inhibition of 1,3-beta-glucan synthesis. The minimum effective concentrations of these compounds against C. albicans and A1. fumigatus ranged from 0.02 to 0.04 microg/ml by microbroth dilution assay, and the IC50 values on C. albicans 1,3-beta-glucan synthase were 0.49, 0.64 and 0.72 microg/ml, respectively. FR209602 and FR209603 showed good efficacy by subcutaneous injection against C. albicans in a murine systemic infection model, with ED50 values of 2.0 and 1.9 mg/kg, respectively.
Kanasaki
Ryuichi
R
Fermentation Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. ryuichi.kanasaki@jp.astellas.com
Abe
Fumie
F
Furukawa
Shigetada
S
Yoshikawa
Koji
K
Fujie
Akihiko
A
Hino
Motohiro
M
Hashimoto
Seiji
S
Hori
Yasuhiro
Y
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D005260:Female; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*
D000935:Antifungal Agents; C511074:FR 209602; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic