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Macrocephatriolides A and B: Two Guaianolide Trimers from Ainsliaea macrocephala as PTP1B Inhibitors and Insulin Sensitizers

文献类型：期刊论文

作者Ren, Yong-Mei1,2,3,5; Zhang, Rui2,3; Feng, Zheling4; Ke, Chang-Qiang2,3; Yao, Sheng2,3; Tang, Chunping2,3; Lin, Ligen4; Ye, Yang1,2,3,5
刊名JOURNAL OF ORGANIC CHEMISTRY
出版日期2021-12-17
卷号86期号:24页码:17782-17789
ISSN号0022-3263
DOI10.1021/acs.joc.1c01996
通讯作者Ye, Yang(yye@simm.ac.cn)
英文摘要Macrocephatriolides A and B (1 and 2), two novel guaiane-type sesquiterpene lactone trimers possessing unique linkage patterns, were identified from the whole plant of Ainsliaea macrocephala. The trimeric architecture of 1 features a cyclohexene linkage and a methylene bridge, which were presumably constructed from three constitutive monomers via a Diels-Alder cycloaddition and a Michael addition, respectively. The three monomers of 2 were tethered by a 1,2-ethanediyl and a methylene linkage at the same time. Their complex structures were established by extensive analysis of spectroscopic data inclusive of band-selective CT-HSQC and CT-HMBC and time-dependent density functional theory (TDDFT) ECD calculations. Compound 2 showed potent inhibition against protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 26.26 +/- 0.88 mu M but not compound 1. In the kinetic study, compound 2 was disclosed as a competitive inhibitor of PTP1B with a K-i value of 16.34 +/- 4.72 pM. In insulin-stimulated C2C12 myotubes, compound 2 dose-dependently enhanced glucose uptake by activating the insulin signaling pathway. Compound 2 might represent a new scaffold of insulin sensitizers.
WOS关键词A-C ; SESQUITERPENE ; SKELETON
资助项目National Natural Science Foundation of China[81903485] ; National Natural Science Foundation of China[82073715] ; National Natural Science Foundation of China[21920102003] ; Science and Technology Development Fund, Macao SAR[FDCT 0031/2019/A1] ; Research Fund of University of Macau[MYRG2018-00037-ICMS] ; Key-Area Research and Development Program of Guangdong Province[2020B0303070002]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000752858300024
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/300445]  
专题新药研究国家重点实验室
通讯作者Ye, Yang
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China
4.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Ren, Yong-Mei,Zhang, Rui,Feng, Zheling,et al. Macrocephatriolides A and B: Two Guaianolide Trimers from Ainsliaea macrocephala as PTP1B Inhibitors and Insulin Sensitizers[J]. JOURNAL OF ORGANIC CHEMISTRY,2021,86(24):17782-17789.
APA Ren, Yong-Mei.,Zhang, Rui.,Feng, Zheling.,Ke, Chang-Qiang.,Yao, Sheng.,...&Ye, Yang.(2021).Macrocephatriolides A and B: Two Guaianolide Trimers from Ainsliaea macrocephala as PTP1B Inhibitors and Insulin Sensitizers.JOURNAL OF ORGANIC CHEMISTRY,86(24),17782-17789.
MLA Ren, Yong-Mei,et al."Macrocephatriolides A and B: Two Guaianolide Trimers from Ainsliaea macrocephala as PTP1B Inhibitors and Insulin Sensitizers".JOURNAL OF ORGANIC CHEMISTRY 86.24(2021):17782-17789.

入库方式： OAI收割

来源：上海药物研究所

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