Inhibitory Effects of N-(3,5-Dimethoxy-4-n-octyloxycinnamoyl)-N′-(3,4-dimethylphenyl)piperazine (YIC-C8-434), an Acyl-CoA:Cholesterol O-Acyltransferase Inhibitor, on Cholesterol Esterification in the Intestine and Liver

The effects of an acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor, N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N′-(3,4-dimethylphenyl)piperazine (YIC-C8-434), on cholesterol esterification in the intestine and liver were investigated in vitro and in vivo. YIC-C8-434 inhibited the formation of cholesteryl [3H]oleate from [3H]oleic acid and cholesterol both in human colon adenocarcinoma Caco2 cells and in human hepatoma HepG2 cells with IC50 values of 0.38 and 0.49 μM, respectively. However, it did not influence the incorporation of [3H]oleic acid into triacylglycerols and phospholipids. Oral administration of YIC-C8-434 at a dose of 8.3 mg/kg/d inhibited [14C]cholesterol absorption by 17% (p