Arborcandins A, B, C, D, E and F, novel 1,3-beta-glucan synthase inhibitors: production and biological activity.
Arborcandins A, B, C, D, E and F, which possess potent 1,3-beta-glucan synthase inhibitory activity, were isolated from the culture broth of a filamentous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, that are structurally different from known glucan synthase inhibitors such as echinocandins. The 1,3-beta-glucan synthases of Candida albicans and Aspergillus fumigatus were inhibited by arborcandins with IC50 ranging from 0.012 to 3 microg/ml. The apparent Ki value of arborcandin C for C. albicans and A. fumigatus were 0.12 microM and 0.016 microM, respectively. The inhibition against these two 1,3-beta-glucan synthases by arborcandin C was noncompetitive. These compounds exhibited potent fungicidal activity against Candida spp. with MIC ranging from 0.25 to 8 microg/ml. The growth of A. fumigatus was suppressed by arborcandins with concentrations ranging from 0.063 to 4 microg/ml.
Ohyama
T
T
Lead Discovery Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan.
Kurihara
Y
Y
Ono
Y
Y
Ishikawa
T
T
Miyakoshi
S
S
Hamano
K
K
Arai
M
M
Suzuki
T
T
Igari
H
H
Suzuki
Y
Y
Inukai
M
M
D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000201:enzymology; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D003455:Cryptococcus neoformans / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D005285:Fermentation; D005658:Fungi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D008565:Membrane Proteins; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029702:Schizosaccharomyces pombe Proteins
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D029702:Schizosaccharomyces pombe Proteins; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase