| Autor: |
Ye, Xiaoli, He, Kai, Zhu, Xiaokang, Zhang, Baoshun, Chen, Xin, Yi, Jun, Li, Xuegang |
| Zdroj: |
Medicinal Chemistry Research; Jul2012, Vol. 21 Issue 7, p1353-1362, 10p |
| Abstrakt: |
From more than 100 simulation-designed compounds, 8-alkyl-berberine derivatives with a long aliphatic chain ( n = 10-20) were chosen and successfully synthesized to evaluate their antihyperlipidemic activity. With elongating the aliphatic chain, the inhibition of derivatives to HMG-CoA reductase (HMGR) and the LD increased gradually. Especially, 8-hexadecyl-berberine ( 4D) with 8.0 μmol/l significantly inhibited HMGR, even higher than lovastatin. Then, the inhibition gradually decreased with the aliphatic chain further elongating. Animal experiments showed that all tested derivatives could improve blood lipid level to different degree. Similarly, compound 4D showed the best lipid-reducing efficiency especially for TC and LDL-c level which were near to those of the normal control, and could recover the liver damage caused by the high-fat and high-cholesterol diet. The interaction between the receptor and the ligand indicated that the improved antihyperlipidemic efficiency of 4D was exerted by a dual mechanism of inhibiting HMGR activity similar with statins and lowering the level of low density lipoprotein-cholesterol (LDL-c) similar with berberine. Thus, it might be a potential antihyperlipidemic drug candidate. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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