biostudies-literatureDuan SMinistry of Science and Technology of the People's Republic of ChinaNational Natural Science Foundation of China386-91https://www.ebi.ac.uk/biostudies/studies/S-EPMC4416425biostudies-literatureUnknown6(4)Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stiACS medicinal chemistry lettersDesign and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.PMC44164252102ZX09103101-0628120257081225022Ren WHuang SHu YZeng LFeng YLeng YDuan SGong JShen YfalseDesign and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, sti2015-01-01T00:00:00Z2015 Apr2025-04-26T07:55:25.901Z2019-03-27T01:50:49ZS-EPMC44164252594155310.1021/acsmedchemlett.5b00007