Mambetisaeva E T, Kosykh V A, Misharin A Iu, Kosenkov E I, Podrez E A, Repin V S
Biokhimiia. 1993 Jul;58(7):1126-32.
The effects of three novel synthetic derivatives of cholesterol with ethoxy (I), aminoethoxy (II), azidoethoxy (III) and toluenesulfonyloxyethoxy (IV) groups in the 3 beta-hydroxy position of cholesterol on cholesterol synthesis as well as on apolipoprotein B and bile acid secretion in cultured rabbit hepatocytes have been studied. 3 beta-(2-hydroxyethoxy)-cholest-5-en (I) was used as a standard. It was found that the inhibiting effect of these compounds on cholesterol synthesis depends on their structure. Compound II (1 microgram/ml), which inhibited acetate incorporation into cholesterol by 30-50%, appeared to be the most effective among the other compounds tested. This derivative had no effect on the production of bile acids. Compound III was less effective, while compound IV had no effect on cholesterol synthesis. All the compounds under study reduced by 20-36% the secretion of the total apolipoprotein B as measured by the enzyme-linked immunosorbent assay (ELISA). None of the synthetic cholesterol derivatives influenced the leucine incorporation into the total protein fraction. The results obtained indicate that 3 beta-(2-aminoethoxy)cholest-5-en, the most effective compound among other cholesterol derivatives tested in the study, can serve as a basis for synthesizing novel cholesterol derivatives able to inhibit cholesterol biosynthesis in liver cells and to decrease the secretion of very low density lipoproteins in cultured rabbit hepatocytes.
研究了胆固醇3β-羟基位置带有乙氧基（I）、氨基乙氧基（II）、叠氮基乙氧基（III）和甲苯磺酰氧基乙氧基（IV）基团的三种新型胆固醇合成衍生物对培养的兔肝细胞中胆固醇合成以及载脂蛋白B和胆汁酸分泌的影响。以3β-(2-羟基乙氧基)-胆甾-5-烯（I）作为标准物。发现这些化合物对胆固醇合成的抑制作用取决于它们的结构。化合物II（1微克/毫升）能使乙酸掺入胆固醇的量减少30 - 50%，在其他受试化合物中似乎是最有效的。该衍生物对胆汁酸的产生没有影响。化合物III效果较差，而化合物IV对胆固醇合成没有影响。通过酶联免疫吸附测定（ELISA）测量，所有研究的化合物都使总载脂蛋白B的分泌减少了20 - 36%。没有一种合成胆固醇衍生物影响亮氨酸掺入总蛋白组分。所得结果表明，3β-(2-氨基乙氧基)胆甾-5-烯是该研究中测试的其他胆固醇衍生物中最有效的化合物，可作为合成新型胆固醇衍生物的基础，这些衍生物能够抑制肝细胞中的胆固醇生物合成，并减少培养的兔肝细胞中极低密度脂蛋白的分泌。
