Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors

被引:117
作者
Asadipour, Ali [1 ]
Alipour, Masoumeh [2 ]
Jafari, Mona [2 ]
Khoobi, Mehdi [2 ]
Emami, Saeed [3 ]
Nadri, Hamid [4 ,5 ]
Sakhteman, Amirhossein [4 ,5 ]
Moradi, Alireza [4 ,5 ]
Sheibani, Vahid [1 ]
Moghadam, Farshad Homayouni [5 ]
Shafiee, Abbas [2 ]
Foroumadi, Alireza [1 ,2 ]
机构
[1] Kerman Univ Med Sci, Neurosci Res Ctr, Kerman, Iran
[2] Univ Tehran Med Sci, Res Ctr, Fac Pharm & Pharmaceut Sci, Dept Med Chem, Tehran, Iran
[3] Mazandaran Univ Med Sci, Fac Pharm, Res Ctr, Dept Med Chem & Pharmaceut Sci, Sari, Iran
[4] Shahid Sadoughi Univ Med Sci, Fac Pharm, Dept Med Chem, Yazd, Iran
[5] Shahid Sadoughi Univ Med Sci, Sch Med, Neurobiomed Res Ctr, Yazd, Iran
基金
美国国家科学基金会;
关键词
Acetylcholinesterase; Butyrylcholinesterase; Coumarin; N-Benzylpiperidine; Alzheimer's disease; Docking; Kinetic study; ALZHEIMERS-DISEASE; HIGHLY POTENT; DESIGN; DERIVATIVES; ACID;
D O I
10.1016/j.ejmech.2013.10.024
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC50 = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:623 / 630
页数:8
相关论文
共 25 条
[1]
Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors [J].
Alipour, Masoumeh ;
Khoobi, Mehdi ;
Foroumadi, Alireza ;
Nadri, Hamid ;
Moradi, Alireza ;
Sakhteman, Amirhossein ;
Ghandi, Mehdi ;
Shafiee, Abbas .
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (24) :7214-7222
[2]
A review on coumarins as acetylcholinesterase inhibitors for Alzheimer's disease [J].
Anand, Preet ;
Singh, Baldev ;
Singh, Nirmal .
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (03) :1175-1180
[3]
Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase [J].
Catto, Marco ;
Pisani, Leonardo ;
Leonetti, Francesco ;
Nicolotti, Orazio ;
Pesce, Paolo ;
Stefanachi, Angela ;
Cellamare, Saverio ;
Carotti, Angelo .
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (01) :146-152
[4]
Dan C., 2012, VIRTUAL SCREENING, P83
[5]
Method for measuring neurotoxicity of aggregating polypeptides with the MTT assay on differentiated neuroblastoma cells [J].
Datki, Z ;
Juhász, A ;
Gálfi, M ;
Soós, K ;
Papp, R ;
Zádori, D ;
Penke, B .
BRAIN RESEARCH BULLETIN, 2003, 62 (03) :223-229
[6]
Design, synthesis and pharmacological evaluation of hybrid molecules out of quinazolinimines and lipoic acid lead to highly potent and selective butyrylcholinesterase inhibitors with antioxidant properties [J].
Decker, Michael ;
Kraus, Birgit ;
Heilmann, Joerg .
BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (08) :4252-4261
[7]
SITE-DIRECTED MUTAGENESIS OF ACTIVE-SITE-RELATED RESIDUES IN TORPEDO ACETYLCHOLINESTERASE - PRESENCE OF A GLUTAMIC-ACID IN THE CATALYTIC TRIAD [J].
DUVAL, N ;
BON, S ;
SILMAN, I ;
SUSSMAN, J ;
MASSOULIE, J .
FEBS LETTERS, 1992, 309 (03) :421-423
[8]
Cholinesterase inhibitors: new roles and therapeutic alternatives [J].
Giacobini, E .
PHARMACOLOGICAL RESEARCH, 2004, 50 (04) :433-440
[9]
Hoerr R, 2002, CNS DRUG REV, V8, P143
[10]
Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental alzheimer therapeutic, dihydrobenzodioxepine cymserine [J].
Kamal, Mohammad A. ;
Klein, Peter ;
Luo, Weiming ;
Li, Yazhou ;
Holloway, Harold W. ;
Tweedie, David ;
Greig, Nigel H. .
NEUROCHEMICAL RESEARCH, 2008, 33 (05) :745-753