Effects of sulfur-containing analogs of stearic acid on growth and fatty acid biosynthesis in the protozoan Crithidia fasciculata

Abstract

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 concentrations. The most potent inhibitor, 8-thiastearic acid (I50 for growth = 0.8 microM; I50 dihydrosterculate synthesis = 0.4 microM), was also observed to inhibit the synthesis of gamma-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.

Increased Serum Level of Cyclopropaneoctanoic Acid 2‐Hexyl in Patients with Hypertriglyceridemia‐Related Disorders

“…These fatty acids (FA) have also been found in certain eukaryotes, including protozoa [2] and plants [3, 4]. However, few studies have documented the presence of CFA in animals [5–7].…”

“…Switching obese individuals to 1 3 species, and likely play a role in the pathogenesis of bacterial infections [1]. These fatty acids (FA) have also been found in certain eukaryotes, including protozoa [2] and plants [3,4]. However, few studies have documented the presence of CFA in animals [5][6][7].…”

Genetic and Chemical Evaluation of Trypanosoma brucei Oleate Desaturase as a Candidate Drug Target

“…The same compounds had been earlier tested on cultures of the trypanosomatids Crithidia fasciculata and Leishmania sp ., although as inhibitors of dihydrosterculic acid biosynthesis. This cyclopropane FA is exclusively synthesized by eukaryotic microbes such as species of Crithidia , Herpetomonas , Leptomonas and Leishmania , but not by trypanosomes or vertebrates, suggesting dihydrosterculic acid biosynthesis as a putative target for selective chemotherapy of leishmaniasis [16], [17]. However, our results (as obtained with T. cruzi ) suggested that the deleterious effect, at least for 10-TS, was most probably due to a specific inhibition of the SCD and a consequent drop in levels of essential FAs such as oleate and linoleate, in the Leishmania 's membranes [13].…”

Cyclopropaneoctanoic Acid 2‐Hexyl Upregulates the Expression of Genes Responsible for Lipid Synthesis and Release in Human Hepatic HepG2 Cells

“…In our previous studies (Mika et al, ; Sledzinski et al, ), we showed that human adipose tissue and serum may contain cyclopropane fatty acids (CFA), previously examined primarily in bacteria, protozoa, and plants (Grogan & Cronan, ; Rahman et al, ; Yu, Prakash, Sweet, & Shanklin, ). Recently, the presence of CFA in humans was also confirmed by other authors, who found elevated levels of these fatty acids in adipose tissue from patients with cancer‐related and primary lymphedema (Sedger et al, ).…”