Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11 beta-HSD1 inhibitors: Potential impact in diabetes
Deng, Xu1; Shen, Yu2; Yang, Jing1,2; He, Juan1; Zhao, Yu1; Peng, Li-Yan1; Leng, Ying2; Zhao, Qin-Shi1
Corresponding AuthorZhao, QS (reprint author), Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China. ; qinshizhao@mail.kib.ac.cn
2013-07-01
Source PublicationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
Volume65Pages:403-414
AbstractThe biological screening of a collection of nature occurring diterpenoids against 11 beta-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11 beta-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11 beta-HSD1) = 9.4 nM and selectivity index (human 11 beta-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11 beta-HSD1 were generated using docking simulations. Based on the results, the structural activity relationships (SARs) of compounds 1b and 2 were also discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.
KeywordEnt-kaurene Diterpenoids Structure-activity Relationship Studies Selective 11 Beta-hsd1 Inhibitors Urea Derivatives Diabetes
Subject AreaChemistry, Medicinal
Indexed BySCI ; IC
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal
WOS IDWOS:000322850100039
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/16751
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
Recommended Citation
GB/T 7714
Deng, Xu,Shen, Yu,Yang, Jing,et al. Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11 beta-HSD1 inhibitors: Potential impact in diabetes[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2013,65:403-414.
APA Deng, Xu.,Shen, Yu.,Yang, Jing.,He, Juan.,Zhao, Yu.,...&Zhao, Qin-Shi.(2013).Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11 beta-HSD1 inhibitors: Potential impact in diabetes.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,65,403-414.
MLA Deng, Xu,et al."Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11 beta-HSD1 inhibitors: Potential impact in diabetes".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 65(2013):403-414.
Files in This Item: Download All
File Name/Size DocType Version Access License
Deng-2013-Discovery (1215KB) 开放获取--View Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Deng, Xu]'s Articles
[Shen, Yu]'s Articles
[Yang, Jing]'s Articles
Baidu academic
Similar articles in Baidu academic
[Deng, Xu]'s Articles
[Shen, Yu]'s Articles
[Yang, Jing]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Deng, Xu]'s Articles
[Shen, Yu]'s Articles
[Yang, Jing]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: Deng-2013-Discovery and struct.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.