Discovery of two ent -atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana .

Euphorlactone A (1), a rare rearranged ent -atisane norditerpenoid with an undescribed 3- nor -2,4-olide- ent -atisane scaffold, and euphorlactone B (2), a new ent -atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana . Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh 2 (OCOCF 3 ) 4 -induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC 50 = 2.13 ± 0.06 μM and K i = 0.058 μM), which was five times stronger than that of the positive control (rivastigmine, IC 50 = 12.46 ± 0.82 μM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.