Anticandidal activity of 5-fluorocytosine-peptide conjugates
- 1 September 1979
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 22 (9) , 1104-1109
- https://doi.org/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-Flurocytosine (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 Saccharomyces cerevisiae 9763, Candida 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.degree. 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.This publication has 2 references indexed in Scilit:
- Peptide transport in yeast: Uptake of radioactive trimethionine in Saccharomyces cerevisiaeArchives of Biochemistry and Biophysics, 1977
- Nucleosides. XXXIII. N4-Acylated 5-Fluorocytosines and a Direct Synthesis of 5-Fluoro-2'-deoxycytidine1Journal of Medicinal Chemistry, 1966