Discovery of two -atisane diterpenoid lactones with AChE inhibitory activity from the roots of

• Published in: Organic & biomolecular chemistry Vol. 21; no. 34; pp. 6949 - 6955
• Main Authors: Wei, Jiangchun, Li, Zhiyue, Shan, Min, Wu, Fengzhi, Li, Limin, Ma, Yucui, Wu, Junhong, Li, Xinping, Liu, Yaqian, Hu, Zhengxi, Zhang, Yonghui, Wu, Zhengzhi
• Format: Journal Article
• Published: 30.08.2023
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d3ob01007d

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. Euphorlactone A ( 1 ), a 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 .