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.