Design, synthesis and biological evaluation of acridone glycosides as selective BChE inhibitors

Ma, Wei; Bi, Jing; Zhao, Chun; Gao, Yangguang; Zhang, Guisheng

doi:10.1016/j.carres.2020.107977

Cited by 15 publications

(2 citation statements)

References 61 publications

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“…Hence, small molecule drugs with molecular weight less than 400 Da and lipid solubility such as the xanthone derivatives synthesised and presented in this study, could potentially cross the BBB and preferred in the drug development for brain diseases 63 . As a summary, eleven xanthone derivatives (5,8,11,17,19,(21)(22)(23)(26)(27)(28) possessed potent AChE inhibition activity. The overall results deduced that 3-O-substituted xanthones that carry a saturated linear hydrocarbon side chain of 4-carbons in chain length with an addition of phenyl group, or diether or ester are beneficial in AChE inhibition activity.…”

Section: Ache and Bche Inhibitory Activitiesmentioning

confidence: 99%

“…Hence, targeting AChE could hinder the production of AChEb-amyloid complexes. The current management of AD is focussing on the enhancement of the concentration of ACh in the synaptic cleft by inhibiting cholinesterase 16,17 . Most of the U.S. Food and Drug Administration (FDA)-approved prescription drugs for AD are AChE inhibitors including Donepezil 18 , Galanthamine 19 , and the dual cholinesterase inhibitor Rivastigmine 20 .…”

Section: Introductionmentioning

confidence: 99%

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New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors

Loh

Kwong

Lam

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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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 IC 50 values ranged 0.88 to 1.28 mM. 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 p-p stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and p-p 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.

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