title: Syntheses of diacyltanshinol derivatives and their suppressive effects on macrophage foam cell formation by reducing oxidized LDL uptake.
abstract: A series of diacyltanshinol derivatives were synthesized by esterifying the corresponding o-hydroquinones of tanshinones. The suppressive effects of the synthesized compounds on oxidized low-density lipoprotein (oxLDL) uptake and oxLDL-induced macrophage-derived foam cell formation were evaluated. Our results indicated that the nicotinate derivatives 1a and 2a, modified from tanshinone IIA and cryptotanshinone, showed stronger suppressive activity on oxLDL uptake and the resultant foam cell formation relative to tanshinone IIA. Western Blot analysis indicated that derivatives 1a and 2a could dose-dependently inhibit the expression of oxLDL-induced LOX-1, implying that the suppressive effects of 1a and 2a on oxLDL uptake and foam cell formation could be at least partially attributed to the inhibition of LOX-1 expression in macrophages.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Da-Li
authors.initials: DL
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Ye
authors.affiliation: Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lssalk@mail.sysu.edu.cn.
authors.forename: Lin-Kun
authors.initials: LK
authors.lastname: An
mesh_terms: D045784:Abietanes / Q000737:chemistry; D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry*; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020011:Protective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors
chemical_list: D045784:Abietanes; D002109:Caffeic Acids; D008077:Lipoproteins, LDL; C495138:Olr1 protein, mouse; D020011:Protective Agents; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; C585969:tanshinol; C021751:tanshinone
keywords: Atherosclerosis; Diacyltanshinol derivative; Foam cell formation; Lipid uptake; Tanshinone