Synthesis and evaluation of substituted 4-methyl-2-oxo-2H-chromen-7-yl phenyl carbamates as potent acetylcholinesterase inhibitors and anti- amnestic agents.
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.
Department of Chemistry, Punjabi University, Patiala-147002, Punjab, India.
Preet
P
Anand
Baldev
B
Singh
D000110:Acetylcholinesterase / Q000378:metabolism*; D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
C000590688:4-methyl-2-oxo-2H-chromen-7-yl (2-nitrophenyl)carbamate; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D048448:Phenylcarbamates; D000110:Acetylcholinesterase