Synthesis and biological activity of novel macrocyclic antifungals: acylated conjugates of the ornithine moiety of the lipopeptidolactone FR901469.
A series of acylated analogues of the novel macrocyclic lipopeptidolactone FR901469 has been prepared and evaluated for antifungal and hemolytic activity. Several analogues displayed markedly reduced hemolytic potential and comparable protective effects to the natural product in a mouse model of candidiasis.
Barrett
D
D
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan. david_barrett@po.fujisawa.co.jp
Tanaka
A
A
Harada
K
K
Ohki
H
H
Watabe
E
E
Maki
K
K
Ikeda
F
F
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002177:Candidiasis / Q000188:drug therapy; D047630:Depsipeptides; D006461:Hemolysis / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D055666:Lipopeptides
D000935:Antifungal Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C417112:FR 901469; D055666:Lipopeptides