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Synthesis of Sordaricin analogues as potent antifungal agents against Candida albicans. 2002
Satoru Kaneko, and
Takuya Uchida, and
Satoshi Shibuya, and
Takeshi Honda, and
Isao Kawamoto, and
Tamako Harasaki, and
Takashi Fukuoka, and
Toshiyuki Konosu
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, 140-8710, Tokyo, Japan. skanek@shina.sankyo.co.jp
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.
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