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 μg mL−1 range, except for these against the least susceptible Candida krusei. The least active conjugates containing C2, C16, or C18 FA were slowly hydrolyzed 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. [Display omitted] •Esterase-labile trimethyl lock system seems to be a suitable linker in Trojan horse strategy against pathogenic fungi.•Fatty acid residues can be applied as molecular carriers in enzymatically cleavable antifungal conjugates.•The advantage of fatty acids as candidates for molecular carriers is their very simple structure and convenient synthesis.•Flucytosine was used as a tool to demonstrate usefulness of fatty acids as molecular carriers.