Development and structure-activity relationships of tanshinones as selective 11beta-hydroxysteroid dehydrogenase 1 inhibitors
文献类型：期刊论文
| 作者 | Deng, Xu1,2; Huang, Su-Ling3 ; Ren, Jian1; Pan, Zheng-Hong1,4; Shen, Yu3; Zhou, Hao-Feng1; Zuo, Zhi-Li1; Leng, Ying3; Zhao, Qin-Shi1
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| 刊名 | Natural products and bioprospecting
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| 出版日期 | 2022-09-22 |
| 卷号 | 12期号:1页码:36 |
| ISSN号 | 2192-2195 |
| 关键词 | Metabolic syndrome Selective 11beta-HSD1 inhibitors Structure-activity relationships Tanshinones |
| DOI | 10.1007/s13659-022-00358-9 |
| 文献子类 | Article |
| 英文摘要 | 11beta-Hydroxysteroid dehydrogenase 1 (11beta-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 11beta-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 11beta-HSD1 inhibitory activity and good selectivity over 11beta-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 11beta-HSD1. Remarkably, compounds 1, 17 and 30 significantly inhibited 11beta-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 11beta-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes, but also expands the boundaries of the chemical and biological spaces of tanshinones. |
| 语种 | 英语 |
| WOS记录号 | MEDLINE:36131216 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309287]  |
| 专题 | 新药研究国家重点实验室 |
| 作者单位 | 1.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China; 2.Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, China; 3.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; 4.Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin, 541006, 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 11beta-hydroxysteroid dehydrogenase 1 inhibitors[J]. Natural products and bioprospecting,2022,12(1):36. |
| 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 11beta-hydroxysteroid dehydrogenase 1 inhibitors.Natural products and bioprospecting,12(1),36. |
| MLA | Deng, Xu,et al."Development and structure-activity relationships of tanshinones as selective 11beta-hydroxysteroid dehydrogenase 1 inhibitors".Natural products and bioprospecting 12.1(2022):36. |
入库方式： OAI收割
来源：上海药物研究所
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