Synthesis and biological activity of novel macrocyclic antifungals. modification of the tyrosine moiety of the lipopeptidolactone FR901469.
A series of tyrosine-modified derivatives of the macrocyclic lipopeptidolactone FR901469 have been prepared and evaluated for in vitro and in vivo antifungal activity and for hemolytic activity towards red blood cells. Compound 14 displayed significantly reduced hemolytic potential at 1mg/mL and a comparable protective effect to FR901469 in a mouse candidiasis model.
Barrett
D
D
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., 2-1-6 Kashima, Yodogawa-ku, 532-8514, Osaka, Japan. david_barrett@po.fujisawa.co.jp
Tanaka
A
A
Harada
K
K
Watabe
E
E
Maki
K
K
Ikeda
F
F
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000166:cytology / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D047630:Depsipeptides; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000592:standards; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry*; D055666:Lipopeptides
D000935:Antifungal Agents; D047630:Depsipeptides; D007783:Lactones; D010456:Peptides, Cyclic; D014443:Tyrosine; C417112:FR 901469; D055666:Lipopeptides