Title
Amaryllidaceae alkaloids with new framework types from Zephyranthes candida as potent acetylcholinesterase inhibitors
Author
Guanqun Zhan, Junjun Liu, Junfei Zhou, Bin Sun, Haji Akber Aisa, Guangmin Yao
Year
2016
Journal
European Journal of Medicinal Chemistry
Abstract
Three new Amaryllidaceae alkaloids, named zephycandidines I−III (1–3), were isolated from Zephyranthes candida. The structures of 1−3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1Hsingle bond1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. The absolute configuration of 1 was finally established by single crystal X-ray diffraction using Cu Kα radiation. Zephycandidines I (1) and III (3) with new framework types represent the first example of 7-phenyl-hexahydroindole and 5,2'-dimethyl-biphenyl-2-ylamine alkaloids, respectively, and their plausible biosynthetic pathway are proposed. Zephycandidine II (2) is the first C3a-phenyl-hexahydroindole type alkaloid isolated from the genus of Zephyranthes. These new alkaloids 1–3 were evaluated for their acetylcholinesterase (AChE) inhibitory activities, and 3 showed potent AChE inhibitory activity with an IC50 value of 8.82 μM, suggesting that the framework of 5,2'-dimethyl-biphenyl-2-ylamine in 3 may be a potential group for the AChE inhibitory activity. The docking studies of 1−3 and galanthamine with AChE revealed that interactions with W286 and Y337 are necessary for the AChE inhibitory activity.
Instrument
J-810
Keywords
Circular dichroism, Absolute configuration, Natural products, Medicinal