Fungistatic Activity, Uptake and Incorporation of 5-Fluorocytosine in Candida albicans, as Influenced by Pyrimidines and Purines. I. Reversal Experiments

Abstract

The fungistatic activity of fluorinated pyrimidines, particularly 5-fluorocytosine (5-FC), and the reversal power of bases and nucleosides of the pyrimidines and purine classes were studied, chiefly in Candida albicans. 5-FC was the most potent antifungal agent, followed by 5-fluorouridine. Cytosine, uridine and adenine were the strongest antagonists of 5-FC activity. A direct correlation, independent of the chemical nature of the antagonists, was found between radiolabelled 5-FC taken up in the yeast cells and inhibition of growth. Except for the anatagonistic effect of some purines, particularly adenine, both antifungal and reversal patterns were compatible with the suggested pathway and mechanism of action of 5-FC (formation of 5-fluorouridylic acid after intracellular deamination of the drug to 5-fluorouracil).