Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors

• Published in: Bioorganic & medicinal chemistry Vol. 20; no. 24; pp. 7214 - 7222
• Main Authors: Alipour, Masoumeh, Khoobi, Mehdi, Foroumadi, Alireza, Nadri, Hamid, Moradi, Alireza, Sakhteman, Amirhossein, Ghandi, Mehdi, Shafiee, Abbas
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.12.2012; Elsevier
• Subjects: Acetylcholinesterase; Actylcholinesterase inhibitor; Animals; Benzylpyridinium; Binding Sites; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Colorimetry; Coumarin; Coumarins - chemistry; Coumarins - pharmacology; donepezil; Drugs; Electrophorus - metabolism; Ellman’s method; Enzymes; inhibitory concentration 50; Life Sciences & Biomedicine; Medical sciences; Models, Molecular; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; pyridinium; Pyridinium Compounds - chemistry; Pyridinium Compounds - pharmacology; Science & Technology; Structure-Activity Relationship; Benzylpyridinium; Ellman’s method; Coumarin; Actylcholinesterase inhibitor; CHOLINERGIC HYPOTHESIS; BUTYRYLCHOLINESTERASE; DESIGN; SERIES; Ellman's method; ALZHEIMERS-DISEASE; BIOLOGICAL EVALUATION; Organic cation; Enzyme; Coumarine derivatives; Benzene derivatives; Enzyme inhibitor; Lactone; Esterases; Binding site; Acetylcholinesterase; Carboxylic ester hydrolases; Hydrolases; Anticholinesterase agent
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.08.052

A novel series of coumarin derivatives linked to benzyl pyridinium group were achieved as potent and dual binding site acetylcholinesterase inhibitors. A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman’s method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC50 in which compound 3r (IC50=0.11nM) was the most active compound against acetylcholinesterase enzyme.