title: FR227244, a novel antifungal antibiotic from Myrothecium cinctum No. 002. II. Biological properties and mode of action.
abstract: FR227244 is a novel triterpene glycoside that exhibits in vitro antifungal activity against filamentous fungi such as Aspergillus sp. and Trichophyton sp. and yeast such as Candida utilis and Candida parapsilosis but shows low activity against Candida albicans, Candida krusei and Candida tropicalis. Specifically, FR227244 exhibits in vitro and in vivo antifungal activity against Aspergillus fumigatus. The minimum effective concentration (MEC) of FR227244 against A. fumigatus FP1305 in a micro-broth dilution test was 0.031 microg/ml. FR227244 showed good efficacy by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED(50)s of 1.9 and 18 mg/kg, respectively. FR227244 inhibited glucan synthesis in a 1,3-beta-glucan synthase assay weakly and in whole cells strongly, but did not effect other macromolecule synthesis, including protein, nucleic acids, mannan and chitin. These results and the effect on hyphal morphology of A. fumigatus suggested that FR227244 showed antifungal activity based on inhibition of glucan synthesis.
authors.affiliation: Fermentation Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. motoo_kobayashi@po.fujisawa.co.jp
authors.forename: Motoo
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sato
authors.forename: Fumie
authors.initials: F
authors.lastname: Abe
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nitta
authors.forename: Michizane
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujie
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hino
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hori
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D001232:Aspergillus fumigatus / Q000187:drug effects; D002175:Candida / Q000145:classification / Q000187:drug effects; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; C498217:FR227244; D006027:Glycosides; D014315:Triterpenes