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Design, synthesis and structural-activity relationship studies of phanginin A derivatives for regulating SIK1-cAMP/CREB signaling to suppress hepatic gluconeogenesis

文献类型：期刊论文

作者Wu, Xing-De2,3,5; Huang, Suling4; Shi, Yu1,4; Shen, Yu4; Tu, Wen-Chao5; Leng, Ying1,4; Zhao, Qin-Shi5
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-03-15
卷号232页码:14
ISSN号0223-5234
关键词Hepatic gluconeogenesis Type 2 diabetes Phanginin A derivatives SIK1 Structural-activity relationship
DOI10.1016/j.ejmech.2022.114171
通讯作者Leng, Ying(yleng@simm.ac.cn) ; Zhao, Qin-Shi(qinshizhao@mail.kib.ac.cn)
英文摘要Persistent activation of hepatic gluconeogenesis is a main cause of fasting hyperglycemia in patients with type 2 diabetes (T2D), and the salt-induced kinase 1 (SIK1) acts as a key modulator in regulating hepatic gluconeogenesis. Recently, we first reported phanginin A (PA, 1), a natural cassane diterpenoid isolated from the seeds of Caesalpinia sappan, exhibited potent anti-diabetic effect through activation of SIK1 and increasing PDE4 activity to inhibit hepatic gluconeogenesis pathway by suppressing the cAMP/PKA/CREB pathway in the liver. In present study, we designed and prepared 25 PA derivatives and their structure-activity relationship (SAR) for gluconeogenesis inhibitory activity were established. Among them, compound 7 exhibited remarkable inhibitory activity on hepatic gluconeogenesis by enhancing the SIK1 phosphorylation and ameliorated the hyperglyceamia of type 2 diabetic mice. Our results supported that compound 7 could be served as a potential candidate for the treatment of T2D. (c) 2022 Elsevier Masson SAS. All rights reserved.
WOS关键词NATURAL-PRODUCTS ; TRANSCRIPTION FACTORS ; HORMONAL-REGULATION ; DITERPENOIDS ; METFORMIN ; SEEDS
资助项目Natural Science Foundation of China[81773611] ; Natural Science Foundation of China[21837003] ; Science and Technology Program of Yunnan province[2019FA037] ; National Science and Technology Major Project-Key New Drug Creation and Manufacturing Program[2018ZX09711002-006-012] ; Science and Technology Commission of Shanghai Municipality[19ZR1467600] ; Top Young Talent of the Ten Thousand Talents Program of Yunnan Province
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:000803062900006
源URL[http://119.78.100.183/handle/2S10ELR8/301370]  
专题新药研究国家重点实验室
通讯作者Leng, Ying; Zhao, Qin-Shi
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Yunnan Minzu Univ, Minist Educ, Kunming 650500, Yunnan, Peoples R China
3.Yunnan Minzu Univ, Key Lab Ethn Med Resource Chem, State Ethn Affairs Commiss, Kunming 650500, Yunnan, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Xing-De,Huang, Suling,Shi, Yu,et al. Design, synthesis and structural-activity relationship studies of phanginin A derivatives for regulating SIK1-cAMP/CREB signaling to suppress hepatic gluconeogenesis[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,232:14.
APA Wu, Xing-De.,Huang, Suling.,Shi, Yu.,Shen, Yu.,Tu, Wen-Chao.,...&Zhao, Qin-Shi.(2022).Design, synthesis and structural-activity relationship studies of phanginin A derivatives for regulating SIK1-cAMP/CREB signaling to suppress hepatic gluconeogenesis.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,232,14.
MLA Wu, Xing-De,et al."Design, synthesis and structural-activity relationship studies of phanginin A derivatives for regulating SIK1-cAMP/CREB signaling to suppress hepatic gluconeogenesis".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 232(2022):14.

入库方式： OAI收割

来源：上海药物研究所

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