Synthesis and structure-activity relationship of 13-hexylberberine analogues as CD36 antagonists.
- Author:
Yinghong LI
;
Li WANG
;
Bin HONG
;
Yanni XU
;
Shuyi SI
;
Jiandong JIANG
;
Danqing SONG
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2010;45(9):1128-33
- CountryChina
- Language:Chinese
-
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.
