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Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors

文献类型：期刊论文

作者Deng,Xu3,4; Huang,Su-Ling2; Ren,Jian4; Pan,Zheng-Hong1,4; Shen,Yu2; Zhou,Hao-Feng4; Zuo,Zhi-Li4; Leng,Ying2; Zhao,Qin-Shi4
刊名Natural Products and Bioprospecting
出版日期2022-09-22
卷号12期号:1
ISSN号2192-2195
关键词Metabolic syndrome Tanshinones Selective 11β-HSD1 inhibitors Structure–activity relationships
DOI10.1007/s13659-022-00358-9
通讯作者Zuo,Zhi-Li(zuozhili@mail.kib.ac.cn) ; Leng,Ying(yleng@simm.ac.cn) ; Zhao,Qin-Shi(qinshizhao@mail.kib.ac.cn)
英文摘要Abstract11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) represents a promising drug target for metabolic syndrome, including obesity and type 2 diabetes. Our initial screen of a collection of natural products from Danshen led to the identification of tanshinones as the potent and selective 11β-HSD1 inhibitors. To improve the druggability and explore the structure–activity relationships (SARs), more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials. More than 10 derivatives exhibited potent in vitro 11β-HSD1 inhibitory activity and good selectivity over 11β-HSD2 across human and mouse species. Based on the biological results, SARs were further discussed, which was also partially rationalized by a molecular docking model of 1 bound to the 11β-HSD1. Remarkably, compounds 1, 17 and 30 significantly inhibited 11β-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice, which merits further investigations as anti-diabetic agents. This study not only provides a series of novel selective 11β-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes, but also expands the boundaries of the chemical and biological spaces of tanshinones.Graphic Abstract
语种英语
出版者Springer Nature Singapore
WOS记录号BMC:10.1007/S13659-022-00358-9
源URL[http://119.78.100.183/handle/2S10ELR8/302354]  
专题中国科学院上海药物研究所
通讯作者Zuo,Zhi-Li; Leng,Ying; Zhao,Qin-Shi
作者单位1.Guangxi Institute of Botany, Chinese Academy of Sciences; Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization
2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences; State Key Laboratory of Drug Research
3.Central South University; Xiangya School of Pharmaceutical Sciences
4.Kunming Institute of Botany, Chinese Academy of Sciences; State Key Laboratory of Phytochemistry and Plant Resources in West China
推荐引用方式
GB/T 7714		 Deng,Xu,Huang,Su-Ling,Ren,Jian,et al. Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors[J]. Natural Products and Bioprospecting,2022,12(1).
APA Deng,Xu.,Huang,Su-Ling.,Ren,Jian.,Pan,Zheng-Hong.,Shen,Yu.,...&Zhao,Qin-Shi.(2022).Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors.Natural Products and Bioprospecting,12(1).
MLA Deng,Xu,et al."Development and structure–activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors".Natural Products and Bioprospecting 12.1(2022).

入库方式： OAI收割

来源：上海药物研究所

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