Publication:
2-Arylbenzofurans from Artocarpus lakoocha and methyl ether analogs with potent cholinesterase inhibitory activity

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Issued Date

2018

Resource Type

Article

File Type

application/pdf

ISSN

2235234

DOI

10.1016/j.ejmech.2017.10.019

Other identifier(s)

2-s2.0-85032904600

Rights Holder(s)

Scopus

Bibliographic Citation

European Journal of Medicinal Chemistry. Vol 143, (2018), p.1301-1311

Suggested Citation

Namdaung U., Athipornchai A., Khammee T., Kuno M., Suksamrarn S. 2-Arylbenzofurans from Artocarpus lakoocha and methyl ether analogs with potent cholinesterase inhibitory activity. European Journal of Medicinal Chemistry. Vol 143, (2018), p.1301-1311. doi:10.1016/j.ejmech.2017.10.019 Retrieved from: https://hdl.handle.net/20.500.14740/3905

Title

2-Arylbenzofurans from Artocarpus lakoocha and methyl ether analogs with potent cholinesterase inhibitory activity

Author(s)

Namdaung U.
 Athipornchai A.
 Khammee T.
 Kuno M.
 Suksamrarn S.

Abstract

In vitro screening for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the Artocarpus lakoocha root-bark extracts revealed interesting results. Bioassay-guided fractionation resulted in the isolation of two new (1 and 2) and six known 2-arylbenzofurans 3–8, along with one stilbenoid 9 and one flavonoid 10. The structures of the isolated compounds were elucidated by UV, IR, 1D- and 2D-NMR and MS spectroscopic data analysis. Compounds 4, 6 and 7 exhibited more potent AChE inhibitory activity (IC50 = 0.87–1.10 μM) than the reference drug, galantamine. Compounds 4, 8 and 9 displayed greater BChE inhibition than the standard drug. The preferential inhibition of BChE over AChE indicated that 4 also showed a promising dual AChE and BChE inhibitor. The synthetic mono-methylated analogs 4a-c and 6a-b were found to be good BChE inhibitors with IC50 values ranging between 0.31 and 1.11 μM. Based on the docking studies, compounds 4 and 6 are well-fitted in the catalytic triad of AChE. Compounds 4 and 6 showed different binding orientations on BChE, and the most potent BChE inhibitor 4 occupied dual binding to both CAS and PAS more efficiently. © 2017 Elsevier Masson SAS

Subject(s)

4 hydroxyartolakoochol
 Acetylcholinesterase
 Artocarpus lakkocha extract
 Artolakoochol
 Benzofuran derivative
 Cholinesterase
 Cholinesterase inhibitor
 Cycloartolakoochol
 Dimethyl ether
 Flavonoid
 Galantamine
 Lakoochin
 Lakoochin A
 Plant extract
 Polycyclic aromatic hydrocarbon derivative
 Stilbenoid
 Unclassified drug
 Benzofuran derivative
 Cholinesterase inhibitor
 Ether derivative
 Article
 Artocarpus lakoocha
 Bark
 Bioassay
 Carbon nuclear magnetic resonance
 Cholinesterase inhibition
 Controlled study
 Drug binding site
 Drug isolation
 Drug potency
 Drug protein binding
 Drug screening
 Fractionation
 Heteronuclear multiple bond correlation
 Heteronuclear multiple quantum coherence
 IC50
 Infrared spectroscopy
 Mass spectrometry
 Medicinal plant
 Molecular docking
 Nonhuman
 Nuclear Overhauser effect
 Plant root
 Proton nuclear magnetic resonance
 Structure activity relation
 Time of flight mass spectrometry
 Ultraviolet spectroscopy
 Artocarpus
 Chemistry
 Metabolism
 Protein conformation
 Acetylcholinesterase
 Artocarpus
 Benzofurans
 Butyrylcholinesterase
 Cholinesterase Inhibitors
 Inhibitory Concentration 50
 Methyl Ethers
 Molecular Docking Simulation
 Protein Conformation

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URI

https://hdl.handle.net/20.500.14740/3905

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Scopus: Year 1983-2021

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