FR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. II. In vitro and in vivo activities.
FR901469 is a water-soluble macrocyclic lipopeptidolactone (C71H116N14O23) that has inhibitory activity against 1,3-beta-glucan synthase and exhibits in vitro and in vivo antifungal activity against both Candida albicans and Aspergillus fumigatus. The MICs of FR901469 against Candida albicans FP633 and Aspergillus fumigatus FP1305 in a micro-broth dilution test were 0.63 and 0.16 microg/ml, respectively. FR901469 showed excellent efficacy by subcutaneous injection against both Candida albicans and Aspergillus fumigatus in a murine systemic infection mode, with ED50s of 0.32 and 0.2 mg/kg, respectively. This compound also showed potent anti-Pneumocystis activity in the nude mice model with experimental Pneumocystis pneumonia. The hemolytic activity of FR901469 towards mouse red blood cells, is about 30-fold weaker than that of amphotericin B.
Fujie
A
A
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
Iwamoto
T
T
Muramatsu
H
H
Okudaira
T
T
Sato
I
I
Furuta
T
T
Tsurumi
Y
Y
Hori
Y
Y
Hino
M
M
Hashimoto
S
S
Okuhara
M
M
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D047630:Depsipeptides; D004195:Disease Models, Animal; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*; D011010:Pneumocystis / Q000187:drug effects; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D055666:Lipopeptides
D000935:Antifungal Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C417112:FR 901469; D055666:Lipopeptides