Effects of sulfur-containing analogues of stearic acid on growth and fatty acid biosynthesis in the protozoan Crithidia fasciculata.
Effects of sulfur-containing analogues of stearic acid on growth and fatty acid biosynthesis in the protozoan Crithidia fasciculata.
复制标题
含硫硬脂酸类似物对原生动物束状短膜藻生长和脂肪酸生物合成的影响。
DOI：
10.1021/jm00403a029
复制
发表时间：
1988
影响因子：
7.3
通讯作者：
PascalJr,RA
中科院分区：
文献类型：
--
作者：
Rahman,MD;Ziering,DL;Mannarelli,SJ;Swartz,KL;Huang,DS;PascalJr,RA
研究了多种硬脂酸类似物对锥虫Crithidia fasciculata生长和脂肪酸生物合成的抑制作用。8-，9-，10-，和11-thiastearic酸被发现抑制合成的环丙烷含脂肪酸dihydrosterculic酸（9，10-亚甲基十八烷酸）在生长培养基中的微摩尔浓度，和所有，但9-thiastearate被发现抑制原生动物在可比的浓度的生长。还观察到最有效的抑制剂8-硫代硬脂酸（生长的f50 = 0.8 µ; IB 0二氢硬脂酸合成= 0.4 µ）在相似浓度下抑制-亚麻酸的合成。发现9-和10-硫代硬脂酸酯的亚砜衍生物对生长或脂肪酸合成几乎没有影响，并且发现3-氨基-1，2-丙二醇的几种长链酰胺具有与它们所衍生的脂肪酸类似的效果。（9，10-亚甲基十八烷酸，1），一种广泛存在于细菌和植物中的环丙烷脂肪酸，123也是许多鞭毛类锥虫磷脂的主要成分，包括利什曼原虫的几种致病性物种，2，3化合物1的存在是这些原生动物的“生物化学特性”之一4-至少对于不合成或不需要环丙烷脂肪酸的哺乳动物而言。如果二氢甾醇酸不仅存在于原生动物中，而且实际上是正常生长所必需的，那么1的生物合成的特异性抑制剂可能是有用的抗寄生虫剂。
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 growthand 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 (f50 for growth= 0.8 µ; IB0 dihydrosterculate synthesis= 0.4 µ), was also observed to inhibit the synthesis of-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.Dihydrosterculic acid (9, 10-methyleneoctadecanoic acid, 1), a cyclopropane fatty acid widely distributed in bacteria and plants, 1 23is also a major constituent of the phospho-lipids of many trypanosomatidflagellates, including several pathogenic species of Leishmania, 2, 3 The presence of compound 1 is one of the “biochemical peculiarities” of these protozoa4—at least with respect to mammals, which do not synthesize or require cyclopropane fatty acids. If dihydrosterculic acid is not merely present in the protozoa but in fact required for normalgrowth, then specific in-hibitors of the biosynthesis of 1 might be useful antiparasitic agents.