Jatrophane Diterpenoids with Kv1.3 Ion Channel Inhibitory Effects from Euphorbia helioscopia

Chemical investigation of bioactive components from the whole plant of Euphorbia helioscopia resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D (1) and helioscopids A-P (2-17), along with 11 known analogues (18-28). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D (1) is the fourth natural diterpenoid with a rare bicyclo[8.3.0]tridecane skeleton. The inhibitory effect of the isolated diterpenoids against Kv1.3 ion channels was evaluated in a human embryonic kidney 293 cell model transfected with plasmid encoding Kv1.3, resulting in the identification of a series of potent Kv1.3 ion channel inhibitors, with the most active ones (2 and 15) showing IC50 values of 0.9 mu M.

Automated summary

In this study, a total of 17 new jatrophane diterpenoids, named heliojatrone D (1) and helioscopids A-P (2-17), were isolated and identified from the whole plant of Euphorbia helioscopia. Additionally, 11 known analogues (18-28) were also found. The inhibitory effect of these compounds against Kv1.3 ion channels was evaluated, and two compounds (2 and 15) showed the most potent activity with IC50 values of 0.9 μM.