Chemical diversity in lipopeptide antifungal antibiotics.
In the course of screening for antifungal antibiotics, we have discovered a novel series of lipopeptide compounds structurally related to, but highly superior to, echinocandin B in terms of their water solubility due to the presence of a sulfate residue. These compounds, WF11899s, WF738s, WF14573s, WF16616 and WF22210, and their derivatives have diversity in their nuclear structures and acyl side chains. The producing strains were classified into two groups, the Coleomycetes group and the Hyphomycetes group. Compound FK463, a derivative of WF11899A, is currently in Phase 3 clinical development as a novel antifungal antibiotic.
Hino
M
M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan.
Fujie
A
A
Iwamoto
T
T
Hori
Y
Y
Hashimoto
M
M
Tsurumi
Y
Y
Sakamoto
K
K
Takase
S
S
Hashimoto
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D054714:Echinocandins; D005656:Fungal Proteins; D005658:Fungi / Q000378:metabolism; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000378:metabolism; D010455:Peptides; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D029702:Schizosaccharomyces pombe Proteins
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D008565:Membrane Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D029702:Schizosaccharomyces pombe Proteins; C453721:WF 16616; C453722:WF 22210; C007572:echinocandin B; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase