title: Effects of sulfur-containing analogues 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.
authors.affiliation: Department of Chemistry, Princeton University, New Jersey 08544.
authors.forename: M D
authors.initials: MD
authors.lastname: Rahman
authors.forename: D L
authors.initials: DL
authors.lastname: Ziering
authors.forename: S J
authors.initials: SJ
authors.lastname: Mannarelli
authors.forename: K L
authors.initials: KL
authors.lastname: Swartz
authors.forename: D S
authors.initials: DS
authors.lastname: Huang
authors.forename: R A
authors.initials: RA
authors.lastname: Pascal
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D003421:Crithidia / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D013229:Stearic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D005227:Fatty Acids; D013229:Stearic Acids; D013440:Sulfides; C029355:dihydrosterculic acid