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Discovery of C-9 modified berberine derivatives as novel lipid-lowering agents
Chemical & Pharmaceutical Bulletin ( IF 1.7 ) Pub Date : 2020-10-22 , DOI: 10.1248/cpb.c20-00453
Dong-Dong Li 1, 2 , Pan Yu 1, 2 , Hui Xu 2 , Zhen-Zhong Wang 3 , Wei Xiao 3 , Lin-Guo Zhao 1, 2
Affiliation  

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.



中文翻译:

C-9修饰的小碱衍生物作为新型降脂剂的发现

小ber碱(BBR)是一种具有多种药理活性的季铵苄基异喹啉生物碱,在药物再利用领域被认为是一种很有前途的降脂剂。特别地,在BBR的C-9位的化学修饰可以显着改善其降脂功效。在这项研究中,通过初步的药理试验合理设计,合成和评估了13种新型BBR衍生物。结果表明,与BBR和辛伐他汀相比,大多数化合物具有更强的降血脂活性。在这些化合物中,化合物2h-12h-2在这四个测试中显示出更好的活性分布,涉及总胆固醇(TCHO),甘油三酸酯(TG)和低密度脂蛋白胆固醇(LDLC)的抑制以及高密度脂蛋白胆固醇(HDLC)的增加。相应地,具有9-O-肉桂部分的BBR类似物可能表现出有效的降脂活性,并且应该被开发为开发类似BBR的降脂剂的重要通用模板。

更新日期:2020-10-28
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