Fatty acids as molecular carriers in cleavable antifungal conjugates

Conjugates composed of C2-18 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 (C8), capric (C10), lauric (C12), or myristic (C14) acid residues were in the 2-64 mu g mL-1 range, except for these against the least susceptible Candida krusei. The least active conjugates containing C2, C16, or C18 FA were slowly hy-drolyzed by esterase and probably poorly taken up by Candida cells, as found for their analogs containing a fluorescent label, Nap-NH2 instead of 5-FC.

Automated summary

Conjugates composed of C2-18 fatty acid residues as carriers and 5-fluorocytosine as an active agent showed good in vitro activity against Candida spp. The most active conjugates containing C8, C10, C12, or C14 acid residues had MIC values in the range of 2-64 mu g mL-1, except for Candida krusei. The less active conjugates containing C2, C16, or C18 fatty acids were slowly hydrolyzed by esterase and poorly taken up by Candida cells, similar to their analogs with a fluorescent label instead of 5-FC.