title: Synthesis of Sordaricin analogues as potent antifungal agents against Candida albicans.
abstract: Sordaricin derivatives possessing a cyclohexane ring appendage attached via an ether, thioether, amine, oxime, ester or amide linkage were synthesized and their antifungal activity was evaluated in vitro. Compounds containing a thioether bond or an oxime bond as a linkage exhibited potent MICs (< or = 0.125 microg/mL) against four Candida albicans strains including azole-low-susceptible strains. They were also active (MIC < or = 0.125 microg/mL) against Candida glabrata. Their in vivo efficacy was confirmed in a murine intravenous infection model with Candida albicans.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, 140-8710, Tokyo, Japan. skanek@shina.sankyo.co.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Kaneko
authors.forename: Takuya
authors.initials: T
authors.lastname: Uchida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shibuya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Honda
authors.forename: Isao
authors.initials: I
authors.lastname: Kawamoto
authors.forename: Tamako
authors.initials: T
authors.lastname: Harasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Konosu
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D004224:Diterpenes; D051379:Mice; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D001952:Bridged-Ring Compounds; D004224:Diterpenes; C116705:sordaricin