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 IC 50 values of 0.9 μM.