Anticandidal activity of 5-fluorocytosine-peptide conjugates.
An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested for antiyeast activity against S. Cerevisiae 9763, C. albicans 1-V, C. albicans WD 18-4, and C. Krusei 1-T. The 5-FC derivatives showed antiyeast activity comparable to 5-FC in all strains except C. krusei 1-T, in which case the compounds were less active. The solution stabilities of 5-FC conjugates at 37 degrees C were tested in the same growth medium used for susceptibility testing. The results indicated a range of stabilities where the half-life (t1/2) = 0.3--17.6 h. These results and those obtained in the susceptibility testing suggest extracellular hydrolysis and indicate that the type of linkage used to conjugate 5-FC to peptides will not provide appropriate compounds to evaluate the peptide-carrier concept.
D000935:Antifungal Agents / Q000138:chemical synthesis*; D002175:Candida / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives*; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis; D005437:Flucytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects
D000935:Antifungal Agents; D004952:Esters; D009842:Oligopeptides; D003596:Cytosine; D005437:Flucytosine