Diterpenoids from <i>Euphorbia fischeriana</i> with Kv1.3 Inhibitory Activity
Cai Qin, Hong-Jing Zha, Shiying Yuan, Xing Sun, Xin Lin, Xinyu Zheng, Ying-Xian Qian, Ru-Feng Xia, Yue-Shan Luo, Zhimian Shi, Jun‐Cheng Su, Luo-Sheng Wan
Abstract
Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed ( 1 – 9 ) and 16 known ( 10 – 25 ) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana . The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.