Fatty Acids as Molecular Carriers in Cleavable Antifungal Conjugates

Conjugates composed of C fatty acid (FA) residues as a molecular carrier and 5-fluorocytosine (5-FC) as an active agent, released upon the action of intracellular esterases on the ester bond between FA and "trimethyl lock" intramolecular linker, demonstrate good in vitro activity against human pathogenic yeasts of Candida spp. The minimal inhibitory concentrations (MIC) values for the most active conjugates containing caprylic (C), capric (C), lauric (C), or myristic (C) acid residues were in the 2-64 μg mL range, except for these against the least susceptible Candida krusei. The least active conjugates containing C, C or C FA were slowly hydrolyzed by esterase and probably poorly taken up by Candida cells, as found for their analogs containing a fluorescent label, Nap-NH instead of 5-FC.