Anticandidal activity of 5-fluorocytosine-peptide conjugates

J Med Chem. 1979 Sep;22(9):1104-9. doi: 10.1021/jm00195a019.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antifungal Agents / chemical synthesis*
  • Candida / drug effects*
  • Cytosine / analogs & derivatives*
  • Drug Stability
  • Esters / chemical synthesis
  • Flucytosine / analogs & derivatives*
  • Flucytosine / chemical synthesis
  • Flucytosine / pharmacology*
  • Hydrolysis
  • Microbial Sensitivity Tests
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology
  • Saccharomyces cerevisiae / drug effects

Substances

  • Antifungal Agents
  • Esters
  • Oligopeptides
  • Cytosine
  • Flucytosine