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标题：Discovery of C-9 Modified Berberine Derivatives as Novel Lipid-Lowering Agents
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作者：Dong-Dong Li ; Pan Yu ; Hui Xu 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2021
卷号：69
期号：1
页码：59-66
DOI：10.1248/cpb.c20-00453
出版社：The Pharmaceutical Society of Japan
摘要：Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9- O -cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.
关键词：berberine;natural product;total cholesterol;triglyceride;low-density lipoprotein cholesterol;high-density lipoprotein cholesterol