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 fr actions. Although it did not induce leakage of intracellular materials from the treated cells, it had inhibitory effects on both endogenous and exogen ous cellular respiration. Moreover, it inhibited mitochondrial respiration of Candida utilis ATCC 42402 using both succinate and cytochrome c as respi ratory 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 mi ght be involved in succinate dehydrogenase, complex II in the mitochondrial electron transport chain of the yeast cells. Judging from the inhibitory e ffect of anhydrofulvic acid on mitochondria detected at pH 7.0, it was post ulated that the antifungal activity at a low pH level might depend on the e levation of drug permeability to the cell membrane under acidic conditions.