The study aimed to synthesize and evaluate substituted 4-methyl-2-oxo-2H-chromen-7-yl phenylcarbamates as
potent acetylcholinesterase (AChE) inhibitors and anti-amnestic agents. The compounds were evaluated for AChE and butyrylcholinesterase
(BuChE) inhibitory activity in rat brain homogenate and plasma, respectively. The most potent test
compound 4d was evaluated for memory testing in scopolamine-induced amnesia. The phenylcarbamate substituted coumarins
(4a-4h) demonstrated more potent AChE inhibitory as compared to parent 7-hydroxy-4-methylcoumarin. The introduction
of phenylcarbamate moiety to coumarin template also significantly increased BuChE inhibitory activity, albeit
less than AChE inhibitory activity with approximate BuChE/AChE selectivity ratio of 20. The compound 4d displayed the
most potent AChE inhibitory activity with IC50 = 13.5 ± 1.7 nM, along with amelioration of amnesia in mice in terms of
restoration of time spent in target quadrant and escap latency time. It is concluded that carbamate derivatives of coumarin
may be employed as potential AChE inhibitors and anti-amnestic agents.
Keywords: Phenylcarbamates, coumarin, Alzheimer’s disease, acetylcholinesterase inhibitors.
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Published on: 31 May, 2013
Page: [694 - 702]