Amaryllidaceae alkaloids with new framework types from Zephyranthes candida as potent acetylcholinesterase inhibitors.
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,1H-1H 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 IC50value 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.
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Guanqun
G
Zhan
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Junjun
J
Liu
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Junfei
J
Zhou
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Bin
B
Sun
The Key Laboratory of Plant Resources and Chemistry of Arid Zone and State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, People's Republic of China.
Haji Akber
HA
Aisa
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: gyap@mail.hust.edu.cn.
Guangmin
G
Yao
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000070378:Amaryllidaceae / Q000737:chemistry*; D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004593:Electrophorus; D062105:Molecular Docking Simulation; D011487:Protein Conformation
D047151:Amaryllidaceae Alkaloids; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase
AChE inhibitory activity; Alzheimer's disease; Amaryllidaceae alkaloids; Docking studies; Zephyranthes candida