title: [Synthesis and structure-activity relationship of 13-hexylberberine analogues as CD36 antagonists].
abstract: Scavenger receptor CD36 could bind and endocytose oxLDL into macrophages which were then differentiated into foam cells that constitute the atherosclerotic lesion core, and was considered to be a potential target to treat atherosclerosis. In the establishment of the compound library of berberine (BBR, 1) analogues, we discovered that 13-hexylberberine (2) showed an antagonistic activity against CD36. Taking 2 as the lead compound, 21 derivatives were synthesized and their antagonistic activities were evaluated via an ELISA-like high-throughput screening (HTS) model. The primary structure-activity relationships were studied. It was indicated that the introduction of suitable groups at the 2- and 3-position of the aromatic ring A or at the 9-position of the aromatic ring D could enhance the activity. Among the 21 studied compounds, 7g bearing a benzyloxyl group at the 9-position provided a highest CD36 antagonistic activity with the IC50 value of 7.7 micromol L(-1). Besides, its antagonistic activity was further verified with Sf9 insect cell HTS model. So berberine analogues are a new family of CD36 receptor antagonists and worthy to be studied further.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ying-hong
authors.initials: YH
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Hong
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Xu
authors.forename: Shu-yi
authors.initials: SY
authors.lastname: Si
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Dan-qing
authors.initials: DQ
authors.lastname: Song
mesh_terms: D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D057166:High-Throughput Screening Assays; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors*; D018411:Spodoptera / Q000166:cytology / Q000821:virology; D013329:Structure-Activity Relationship
chemical_list: D018955:CD36 Antigens; D051116:Receptors, Scavenger; D001599:Berberine