7770-78-7Relevant articles and documents
Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors
Butts, Craig P.,Collingridge, Graham L.,Jane, David E.,Mallah, Shahida,Molnár, Elek,Re?nik, Lisa-Maria,Thatcher, Robert J.,Willis, Christine L.
supporting information, p. 9154 - 9162 (2021/11/16)
(-)-Arctigenin and a series of new analogues have been synthesised and then tested for their potential as AMPA and kainate receptor antagonists of human homomeric GluA1 and GluK2 receptors expressed in HEK293 cells using a Ca2+ influx assay. In general, these compounds showed antagonist activity at both receptors with greater activity evident at AMPARs. Schild analysis indicates that a spirocyclic analogue 6c acts as a non-competitive antagonist. Molecular docking studies in which 6c was docked into the X-ray crystal structure of the GluA2 tetramer suggest that (-)-arctigenin and its analogues bind in the transmembrane domain in a similar manner to the known AMPA receptor non-competitive antagonists GYKI53655 and the antiepileptic drug perampanel. The arctigenin derivatives described herein may serve as novel leads for the development of drugs for the treatment of epilepsy. This journal is
Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders
Duan, Shudong,Huang, Suling,Gong, Jian,Shen, Yu,Zeng, Limin,Feng, Ying,Ren, Wenming,Leng, Ying,Hu, Youhong
, p. 386 - 391 (2015/04/27)
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, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.
Identification and characterization of human UDP-glucuronosyltransferases responsible for the in-vitro glucuronidation of arctigenin
Xin, Hong,Xia, Yang-Liu,Hou, Jie,Wang, Ping,He, Wei,Yang, Ling,Ge, Guang-Bo,Xu, Wei
, p. 1673 - 1681 (2016/01/26)
Objectives This study aimed to characterize the glucuronidation pathway of arctigenin (AR) in human liver microsomes (HLM) and human intestine microsomes (HIM). Methods HLM and HIM incubation systems were employed to catalyse the formation of AR glucuronide. The glucuronidation activity of commercially recombinant UGT isoforms towards AR was screened. A combination of chemical inhibition assay and kinetic analysis was used to determine the UGT isoforms involved in the glucuronidation of AR in HLM and HIM. Key findings AR could be extensively metabolized to one mono-glucuronide in HLM and HIM. The mono-glucuronide was biosynthesized and characterized as 4′-O-glucuronide. UGT1A1, 1A3, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7 and 2B17 participated in the formation of 4′-O-G, while UGT2B17 demonstrated the highest catalytic activity in this biotransformation. Both kinetic analysis and chemical inhibition assays demonstrated that UGT1A9, UGT2B7 and UGT2B17 played important roles in AR-4′-O-glucuronidation in HLM. Furthermore, HIM demonstrated moderate efficiency for AR-4′-O-glucuronidation, implying that AR may undergo a first-pass metabolism during the absorption process. Conclusion UGT1A9, UGT2B7 and UGT2B17 were the major isoforms responsible for the 4′-O-glucuronidation of AR in HLM, while UGT2B7 and UGT2B17 were the major contributors to this biotransformation in HIM.
