Mode of action of anhydrofulvic acid against Candida utilis ATCC 42402 under acidic condition.
The mode of action of anhydrofulvic acid against Candida utilis ATCC 42402 was investigated under acidic conditions. Anhydrofulvic acid inhibited the incorporation of radioactive precursors into DNA, RNA, protein and lipid fractions. Although it did not induce leakage of intracellular materials from the treated cells, it had inhibitory effects on both endogenous and exogenous cellular respiration. Moreover, it inhibited mitochondrial respiration of Candida utilis ATCC 42402 using both succinate and cytochrome c as respiratory substrates, but not using NADH. Unexpectedly, the inhibition against isolated mitochondria was observed at pH 7.0. These results suggested that the action site against the respiratory inhibition of anhydrofulvic acid might be involved in succinate dehydrogenase, complex II in the mitochondrial electron transport chain of the yeast cells. Judging from the inhibitory effect of anhydrofulvic acid on mitochondria detected at pH 7.0, it was postulated that the antifungal activity at a low pH level might depend on the elevation of drug permeability to the cell membrane under acidic conditions.
Fujita
K
K
Department of Bio- and Geoscience, Graduate School of Science, Osaka City University, Osaka, Japan.
Nagamine
Y
Y
Ping
X
X
Taniguchi
M
M
D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D002867:Chromones / Q000302:isolation & purification / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects
D000935:Antifungal Agents; D001578:Benzopyrans; D002867:Chromones; C121904:anhydrofulvic acid; C005023:fulvic acid