Cyclandelate. An inhibitor of cholesterol esterification.
In an in vitro study the action of cyclandelate on cholesterol metabolism was investigated. The addition of cyclandelate (100 mumol/L) inhibited the incorporation of acetate into sterol but not into fatty acid in human fibroblasts incubated with the drug for 3 hours. Further exposure of fibroblasts to cyclandelate for 17 hours resulted in a similar inhibition in the uptake and hydrolysis of LDL. Moreover, in the presence of cyclandelate (100 mumol/L), cholesterol esterification was inhibited by 90% in fibroblasts cultured with LDL and in human monocyte derived macrophages cultured with acetyl-LDL. It is likely that the inhibition by cyclandelate of cholesterol esterification in whole cells is due to a direct inhibition of the hepatic microsomal enzyme acyl coenzyme A: cholesterol acyl transferase (ACAT), since addition of the drug in a concentration of 100 mumol/L inhibited by 74% the activity of ACAT derived from rat liver. Furthermore, the intact drug molecule was required for maximal inhibition of microsomal ACAT.
D000818:Animals; D000924:Anticholesteremic Agents; D002788:Cholesterol Esters / Q000378:metabolism*; D003495:Cyclandelate / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood; D008333:Mandelic Acids / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D000924:Anticholesteremic Agents; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D008333:Mandelic Acids; D003495:Cyclandelate