New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors
A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of t...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2021-01-01
|
Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/14756366.2021.1882452 |
id |
doaj-b426022c0bd84b398e44a85d921c2c58 |
---|---|
record_format |
Article |
spelling |
doaj-b426022c0bd84b398e44a85d921c2c582021-02-18T10:31:39ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136162763910.1080/14756366.2021.18824521882452New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitorsZi Han Loh0Huey Chong Kwong1Kok Wai Lam2Soek Sin Teh3Gwendoline Cheng Lian Ee4Ching Kheng Quah5Anthony Siong Hock Ho6Siau Hui Mah7School of Biosciences, Taylor’s University, Lakeside CampusSchool of Chemical Sciences, Universiti Sains MalaysiaDrug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan MalaysiaEnergy and Environment Unit, Engineering and Processing Division, Malaysian Palm Oil BoardDepartment of Chemistry, Faculty of Science, University Putra MalaysiaX-ray Crystallography Unit, School of Physics, Universiti Sains MalaysiaSchool of Biosciences, Taylor’s University, Lakeside CampusSchool of Biosciences, Taylor’s University, Lakeside CampusA new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π–π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π–π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.http://dx.doi.org/10.1080/14756366.2021.1882452alzheimer’s diseaseenzyme kinetic studymolecular dockingsynthesisstructure–activity relationship study |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zi Han Loh Huey Chong Kwong Kok Wai Lam Soek Sin Teh Gwendoline Cheng Lian Ee Ching Kheng Quah Anthony Siong Hock Ho Siau Hui Mah |
spellingShingle |
Zi Han Loh Huey Chong Kwong Kok Wai Lam Soek Sin Teh Gwendoline Cheng Lian Ee Ching Kheng Quah Anthony Siong Hock Ho Siau Hui Mah New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry alzheimer’s disease enzyme kinetic study molecular docking synthesis structure–activity relationship study |
author_facet |
Zi Han Loh Huey Chong Kwong Kok Wai Lam Soek Sin Teh Gwendoline Cheng Lian Ee Ching Kheng Quah Anthony Siong Hock Ho Siau Hui Mah |
author_sort |
Zi Han Loh |
title |
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
title_short |
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
title_full |
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
title_fullStr |
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
title_full_unstemmed |
New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
title_sort |
new 3-o-substituted xanthone derivatives as promising acetylcholinesterase inhibitors |
publisher |
Taylor & Francis Group |
series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
issn |
1475-6366 1475-6374 |
publishDate |
2021-01-01 |
description |
A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π–π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π–π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors. |
topic |
alzheimer’s disease enzyme kinetic study molecular docking synthesis structure–activity relationship study |
url |
http://dx.doi.org/10.1080/14756366.2021.1882452 |
work_keys_str_mv |
AT zihanloh new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT hueychongkwong new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT kokwailam new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT soeksinteh new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT gwendolinechenglianee new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT chingkhengquah new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT anthonysionghockho new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors AT siauhuimah new3osubstitutedxanthonederivativesaspromisingacetylcholinesteraseinhibitors |
_version_ |
1724263592163803136 |