title: Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.
abstract: A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Sida
authors.initials: S
authors.lastname: Shen
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhuang
authors.forename: Yijia
authors.initials: Y
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Lei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004952:Esters; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D032446:Myoblasts / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D004952:Esters; D005663:Furans; D017705:Lignans; D055372:AMP-Activated Protein Kinases; C071942:arctigenin