H. Bossche
Feb 15, 1974
Citations
0
Influential Citations
117
Citations
Quality indicators
Journal
Biochemical Pharmacology
Abstract
Abstract The antifungal and antibacterial drug miconazole has been shown to inhibit, at concentrations lower than those affecting growth, the transport of adenine, guanine and hypoxanthine by Candida albicans in suspension culture. The decrease in the incorporation of purines into nucleic acids seems to be the consequence of an inhibitory effect on their uptake into the cells. When the purines were replaced by adenosine, deoxyadenosine and guanosine, miconazole increased the uptake and incorporation of the radioactivity derived from the nucleosides into macromolecules. The data suggest that the drug-induced increase of nucleoside incorporation into nucleic acids is secondary to enhanced nucleoside transport. Miconazole also slightly affected the uptake of orotic acid. The transport of glucose, glycine and leucine was not affected by miconazole whereas in some way the drug affected glutamine uptake. Studies on the distribution of miconazole and/or its metabolites in the Candida cell indicate that in log-phase cells most of the radioactivity was found in the fraction containing cell walls and plasmalemma. In stationary-phase cells the highest radioactivity was found in the fraction which contained the microsomes. Although more information will be needed, the data presented indicate that at low concentrations, miconazole acts primarily on the yeast cell membranes (cell wall and plasmalemma) resulting in a selective inhibition of the uptake of precursors of RNA and DNA (purines) and mucopolysaccharide (glutamine). Higher doses and longer incubation periods also alter the activities of microsomal membranes.