Inhibition of 11β-HSD1 by Tetracyclic Triterpenoids from Euphorbia kansui

Molecules

Jie Guo²  Li-Yan Zhou²  Hong-Ping He³  Ying Leng¹  Zhen Yang² 

[1] Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, Guangdong, China;State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, Yunnan, China;

关键词: tetracyclic triterpenoids;    Euphorbia kansui;    inhibition of 11β-HSD1;    docking;   

DOI  :  10.3390/molecules171011826

来源: mdpi

【 摘 要 】

The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3β,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were elucidated on the basis of physical and spectral techniques (1D-, 2D-NMR and MS, respectively). Furthermore, these compounds 1–6 exhibited strong inhibitory activity against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), with IC₅₀ values of 34.86 nM, 1.115 μM, 16.08 nM, 2.815 nM, 26.47 nM, 15.99 nM, and 41.86 nM, respectively. The docking results show that the ring part of compounds can insert into the hydrophobic core of h11β-HSD1 and the alkane chain orientates toward the outside. The results presented herein provide a scientific explanation for the usage of the E. kansui in clinical treatment of diabetes.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.