| Abstract: | 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. |
