A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase. II. mode of Action.
1992; Springer Nature; Volume: 45; Issue: 2 Linguagem: Inglês
10.7164/antibiotics.45.160
ISSN1881-1469
AutoresYuhko Aoki, Toshikazu Yamazaki, Masumi Kondoh, Yuri Sudoh, Noboru Nakayama, Yuzuru Sekine, H Shimada, Mikio Arisawa,
Tópico(s)Steroid Chemistry and Biochemistry
ResumoFrom 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.
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