Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation.
Currently there is no approved medicine for the treatment of metabolic syndrome. A series of new derivatives of berberine (BBR) or pseudoberberine (1) was synthesized and evaluated for their activity on AMP-activated protein kinase (AMPK) activation and up-regulatory low-density-lipoprotein receptor (LDLR) gene expression, respectively. In addition, the four major metabolites of BBR in vivo were also examined for their activity on AMPK in order to further understand the chemical mechanisms responsible for its glucose-lowering efficacy. Among those BBR analogues, compound 1 exhibited the potential effect on AMPK activation and LDLR up-regulation as compared with BBR. The results suggested that compound 1 might be a multiple-target agent for the treatment of metabolic syndrome, and thus was selected as a promising drug candidate for further development.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yan-Xiang
YX
Wang
Wei-Jia
WJ
Kong
Ying-Hong
YH
Li
Sheng
S
Tang
Zheng
Z
Li
Yang-Biao
YB
Li
Yong-Qiang
YQ
Shan
Chong-Wen
CW
Bi
Jian-Dong
JD
Jiang
Dan-Qing
DQ
Song
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015854:Up-Regulation / Q000187:drug effects
D001600:Berberine Alkaloids; D011973:Receptors, LDL; C578968:pseudoberberine; D001599:Berberine; D055372:AMP-Activated Protein Kinases