Effects of Sulfur-Containing Analogues of Stearic Acid on Growth and Fatty Acid Biosynthesis in the Protozoan Crithidia Fasciculata

A variety of analogues of stearic acid in which one of the methylene groups was replaced by a sulfur atom were examined as inhibitors of growth and fatty acid biosynthesis in the trypanosomatid protozoan Crithidia fasciculata. The 8-, 9-, 10-, and 11-thiastearic acids were found to suppress the synthesis of the cyclopropane-containing fatty acid dihydrosterculic acid (9,10-methyleneoctadecanoic acid) at micromolar concentrations in the growth medium, and all but the 9-thiastearate were found to inhibit the growth of the protozoa at comparable concentrations. The most potent inhibitor, 8-thiastearic acid (I₅₀ for growth = 0.8 μM; I₅₀ dihydrosterculate synthesis = 0.4 μM), was also observed to inhibit the synthesis of γ-linolenic acid at a similar concentration. The sulfoxide derivatives of the 9- and 10-thiastearates were found to have little effect on growth or fatty acid synthesis, and several long-chain amides of 3-amino-1,2-propanediol were found to have effects similar to those of the fatty acids from which they were derived.