Pleofungins, novel inositol phosphorylceramide synthase inhibitors, from Phoma sp. SANK 13899. I. Taxonomy, fermentation, isolation, and biological activities.
In the course of a screening for inositol phosphorylceramide (IPC) synthase inhibitors, the novel inhibitors pleofungins A, B, C, and D were found in a mycelial extract of a fungus, Phoma sp. SANK13899. Purification was performed by 50% methanol and ethyl acetate extraction, reversed phase open-column chromatography, and HPLC separations. Pleofungin A inhibited the IPC synthase of Saccharomyces cerevisiae and Aspergillus fumigatus at IC(50) values of 16 and 1.0 ng/ml, respectively. The inhibitor also suppressed the growth of Candida albicans, Cryptococcus neoformans, and A. fumigatus at MIC values of 2.0, 0.3, and 0.5 mug/ml, respectively. These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A. fumigatus.
Yano
Tatsuya
T
Lead Discovery Research Laboratories, Sankyo Co., Ltd., Hiromachi, Tokyo, Japan. tyyano@sankyo.co.jp
Aoyagi
Azusa
A
Kozuma
Shiho
S
Kawamura
Yoko
Y
Tanaka
Isshin
I
Suzuki
Yasuhiro
Y
Takamatsu
Yasuyuki
Y
Takatsu
Toshio
T
Inukai
Masatoshi
M
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001203:Ascomycota / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000201:enzymology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002851:Chromatography, High Pressure Liquid; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development; D047630:Depsipeptides / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005285:Fermentation; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology; D013107:Sphingolipids / Q000096:biosynthesis
D000935:Antifungal Agents; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D013107:Sphingolipids; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase