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 Xu2; Huang Suling1 ; Ren Jian2; Pan Zhenghong2; Shen Yu1; Zhou Haofeng2; Zuo Zhili2; Leng Ying1; Zhao Qinshi2
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| 刊名 | NATURAL PRODUCTS AND BIOPROSPECTING
 |
| 出版日期 | 2022 |
| 卷号 | 12期号:6页码:1 |
| ISSN号 | 2192-2195 |
| 关键词 | Metabolic syndrome Tanshinones Selective 11β-HSD1 inhibitors Structure-activity relationships |
| 英文摘要 | 11β-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. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304800]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Deng Xu,Huang Suling,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(6):1. |
| APA | Deng Xu.,Huang Suling.,Ren Jian.,Pan Zhenghong.,Shen Yu.,...&Zhao Qinshi.(2022).Development and structure-activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors.NATURAL PRODUCTS AND BIOPROSPECTING,12(6),1. |
| MLA | Deng Xu,et al."Development and structure-activity relationships of tanshinones as selective 11β-hydroxysteroid dehydrogenase 1 inhibitors".NATURAL PRODUCTS AND BIOPROSPECTING 12.6(2022):1. |
入库方式： OAI收割
来源：上海药物研究所
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