Lok J B, Morris R A, Sani B P, Shealy Y F, Donnelly J J
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia.
Trop Med Parasitol. 1990 Jun;41(2):169-73.
A series of synthetic retinoids was screened for the ability to inhibit the third-to fourth-stage larval molt by Onchocerca lienalis in vitro. Of the 14 retinoids tested, eight gave significant inhibition of the molt at a concentration of 30.6 microM or less. Probit analysis of dose-response data collected for these active compounds indicated values for ED50 in the range of 3.7-17.1 microM. In general, the most active of these N-substituted retinamides were those with small alkyl or monohydroxy alkyl substituents. The most active of these was all-trans-N-(2-hydroxyethyl)retinamide with an ED50 of 3.7 microM. Both the all-trans and 13-cis isomers of the alkyl substituted derivatives were active, the all-trans-N-hydroxyethyl derivative being approximately 5 times as active as the corresponding 13-cis isomer. The N-2,3 dihydroxypropyl derivative, two derivatives with aromatic side chains and three N-(retinoyl)amino acids were inactive by the criteria set in the initial screening. There was no strict correlation between growth regulating activity against O. lienalis and binding affinity for a retinol binding protein from Onchocerca gibsoni.
对一系列合成类视黄醇进行了体外抑制链尾盘尾丝虫第三期至第四期幼虫蜕皮能力的筛选。在测试的14种类视黄醇中，有8种在浓度为30.6微摩尔或更低时对蜕皮有显著抑制作用。对这些活性化合物收集的剂量-反应数据进行的概率分析表明，半数有效剂量（ED50）值在3.7-17.1微摩尔范围内。一般来说，这些N-取代视黄酰胺中活性最高的是那些具有小烷基或单羟基烷基取代基的化合物。其中活性最高的是全反式-N-(2-羟乙基)视黄酰胺，其ED50为3.7微摩尔。烷基取代衍生物的全反式和顺式-13异构体均有活性，全反式-N-羟乙基衍生物的活性约为相应顺式-13异构体的5倍。根据初始筛选设定的标准，N-2,3-二羟丙基衍生物、两种带有芳香侧链的衍生物和三种N-(视黄酰基)氨基酸无活性。对链尾盘尾丝虫的生长调节活性与对吉氏盘尾丝虫视黄醇结合蛋白的结合亲和力之间没有严格的相关性。
