A NEW SERIES OF NATURAL ANTIFUNGALS THAT INHIBIT P450 LANOSTEROL C-14 DEMETHYLASE .2. MODE OF ACTION

被引:25
作者
AOKI, Y
YAMAZAKI, T
KONDOH, M
SUDOH, Y
NAKAYAMA, N
SEKINE, Y
SHIMADA, H
ARISAWA, M
机构
[1] Nippon Roche Research Center, Kamakura 247
关键词
D O I
10.7164/antibiotics.45.160
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
From a Penicillium sp. we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain. We elucidated the mode of action of Ro 09-1470, the most active compound of the series. Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed. P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum. We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.
引用
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页码:160 / 170
页数:11
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