title: Human acyl-CoA: cholesterol acyltransferase inhibitory activities of aliphatic acid amides from Zanthoxylum piperitum DC.
abstract: Acyl-CoA: cholesterol acyltransferase (ACAT) plays an important role in the esterification of cholesterol with its substrates, cholesterol and fatty acyl coenzyme A, to facilitate both intracellular storage and intercellular transport. ACAT-1 is more involved in macrophage foam cell formation and ACAT-2 plays a critical role in the cholesterol absorption process in intestinal enterocytes. Three aliphatic acid amides, beta-sanshool (1), gamma-sanshool (2), and hydroxy-beta-sanshool (3), were isolated by bioassay-guided fractionation of the ethanolic extracts of Zanthoxylum piperitum DC. Compounds 1 and 2 inhibited human ACAT-1 and -2 activities with IC50 values of 39.0 and 79.7 microM for 1 and of 12.0 and 82.6 microM for 2, respectively. However, the hACAT-1 and -2 inhibitory activities of compound 3 having hydroxyl group were relatively less than those of compounds 1 and 2. A semi-synthetic compound 4, which has acetyl residue at 2'-OH of compound 3, exhibited the increased hACAT-1 and -2 inhibitory activities with IC50 values of 28.1 and 87.5 microM, respectively.
authors.affiliation: National Research Laboratory of Lipid Metabolism & Atherosclerosis, KRIBB, Daejeon, Republic of Korea.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Park
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Sojin
authors.initials: S
authors.lastname: An
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
mesh_terms: D000577:Amides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018547:Plant Stems; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D005227:Fatty Acids; C100574:sanshool; D002785:Sterol O-Acyltransferase