中文摘要：

清道夫受体CD36通过结合并内吞氧化低密度脂蛋白（oxLDL）使巨噬细胞泡沫化从而形成动脉粥样硬化的病灶中心,被广泛认为是治疗动脉粥样硬化的潜在靶点。13-己基小檗碱（2）对清道夫受体CD36显示拮抗活性,本研究以其为先导化合物,设计合成了21个2的类似物,应用ELISA-like高通量筛选模型对其CD36拮抗活性进行了评价。初步构效关系结果表明：在A环2和3位或D环9位引入适当的基团均可提高化合物的活性。在21个类似物中,化合物7g（9位为苄氧基）的CD36拮抗活性最高,其IC50为7.7μmol·L-1。此外,7g的CD36拮抗活性也在另一高通量筛选模型中得到了验证。因此,小檗碱衍生物是一类新型的CD36受体拮抗剂,值得进一步研究。

英文摘要：

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 μmol·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.