Synthesis and evaluation of N-substituted 1,4-oxazepanyl Sordaricins as selective fungal EF-2 inhibitors.
Sordaricin analogues possessing 6-methoxy-7-methyl-1,4-oxazepane moiety instead of the sugar part were synthesized and evaluated. It was found that N-substituents on the oxazepane ring had influence on biological activity. In particular, N-(2-methylpropenyl) derivative 12p exhibited potent in vitro antifungal activity. Furthermore, 12p maintained significant activity (MIC 0.25 microg/mL) against Candida albicans SANK51486 even in the presence of 20% horse serum.
Kaneko
Satoru
S
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. skanek@shina.sankyo.co.jp
Arai
Masami
M
Uchida
Takuya
T
Harasaki
Tamako
T
Fukuoka
Takashi
T
Konosu
Toshiyuki
T
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000145:classification / Q000187:drug effects / Q000254:growth & development; D004224:Diterpenes; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D020652:Peptide Elongation Factor 2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D004224:Diterpenes; D020652:Peptide Elongation Factor 2; C116705:sordaricin