Synthesis, docking study, and biological evaluation of novel umbellipherone/hymecromone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors

被引：19

作者：

Moradi, Alireza ^{[1
]}

Faraji, Laleh ^{[2
]}

Nadri, Hamid ^{[1
]}

Hasanpour, Zeinab ^{[2
]}

Moghadam, Farshad H. ^{[3
]}

Pakseresht, Bahar ^{[1
]}

Golshani, Mostafa ^{[2
]}

Moghimi, Setareh ^{[2
]}

Ramazani, Ali ^{[4
]}

Firoozpour, Loghman ^{[2
]}

Khoobi, Mehdi ^{[2
,5
,6
]}

Foroumadi, Alireza ^{[7
,8
,9
]}

机构：

[1] Shahid Sadoughi Univ Med Sci, Dept Med Chem, Fac Pharm, Yazd, Iran

[2] Univ Tehran Med Sci, Inst Pharmaceut Sci TIPS, Tehran, Iran

[3] ACECR, Royan Inst Biotechnol, Cell Sci Res Ctr, Dept Cellular Biotechnol, Esfahan, Iran

[4] Univ Zanjan, Dept Chem, POB 45195-313, Zanjan, Iran

[5] Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biomat, Tehran, Iran

[6] Univ Tehran Med Sci, Fac Pharm, Med Biomat Res Ctr, Tehran, Iran

[7] Univ Tehran Med Sci, Dept Med Chem, Fac Pharm, Tehran, Iran

[8] Kerman Univ Med Sci, Fac Pharm, Dept Med Chem, Kerman, Iran

[9] Kerman Univ Med Sci, Inst Neuropharmacol, Neurosci Res Ctr, Kerman, Iran

来源：

MEDICINAL CHEMISTRY RESEARCH | 2018年 / 27卷 / 07期

基金：

美国国家科学基金会;

关键词：

Alzheimer's disease; Cholinesterase inhibitor; Docking; Umbellipherone derivatives; ALZHEIMERS-DISEASE; AMYLOID-BETA; ACETYLCHOLINESTERASE INHIBITORS; TARGET; TAU; COUMARINS; PROTEINS; DESIGN; SYSTEM; DRUG;

D O I：

10.1007/s00044-018-2187-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel hybrid series of umbellipherone and benzyl amine scaffolds, linked via triazole ring, was synthesized and evaluated as both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Most of the synthesized compounds showed moderate to high activities by using Ellman's modified assay. Among the target compounds, 6e bearing 3-methoxy substituent on benzyl moiety was the most active one (AChE and BuChE IC50 = 3.4 and 1.1 mu M, respectively). Finally, binding modes of the target compound was studied using molecular docking stimulations. The neuroprotectivity evaluation exhibited that this compound efficiently protected PC12 neurons against H2O2-induced cell death.

引用

页码：1741 / 1747

页数：7

共 32 条

[11] Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease [J].

Duan, Songwei ;

Guan, Xiaoyin ;

Lin, Runxuan ;

Liu, Xincheng ;

Yan, Ying ;

Lin, Ruibang ;

Zhang, Tianqi ;

Chen, Xueman ;

Huang, Jiaqi ;

Sun, Xicui ;

Li, Qingqing ;

Fang, Shaoliang ;

Xu, Jun ;

Yao, Zhibin ;

Gu, Huaiyu .

NEUROBIOLOGY OF AGING, 2015, 36 (05) :1792-1807

[12] Acetylcholinesterase: From 3D structure to function [J].

Dvir, Hay ;

Silman, Israel ;

Harel, Michal ;

Rosenberry, Terrone L. ;

Sussman, Joel L. .

CHEMICO-BIOLOGICAL INTERACTIONS, 2010, 187 (1-3) :10-22

[13] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

[14] The role of tau in neurodegeneration [J].

Gendron, Tania F. ;

Petrucelli, Leonard .

MOLECULAR NEURODEGENERATION, 2009, 4

[15]

Greig NH, 2001, CURR MED RES OPIN, V17, P159

[16] Butyrylcholinesterase: An important new target in Alzheimer's disease therapy [J].

Greig, NH ;

Lahiri, DK ;

Sambamurti, K .

INTERNATIONAL PSYCHOGERIATRICS, 2002, 14 :77-91

[17] Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates [J].

Himo, F ;

Lovell, T ;

Hilgraf, R ;

Rostovtsev, VV ;

Noodleman, L ;

Sharpless, KB ;

Fokin, VV .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (01) :210-216

[18] Nuclear Tau and Its Potential Role in Alzheimer's Disease [J].

Maina, Mahmoud Bukar ;

Al-Hilaly, Youssra K. ;

Serpell, Louise C. .

BIOMOLECULES, 2016, 6 (01) :2-20

[19] O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: Multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation [J].

Mao, Fei ;

Huang, Ling ;

Luo, Zonghua ;

Liu, Anqiu ;

Lu, Chuanjun ;

Xie, Zhiyong ;

Li, Xingshu .

BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (19) :5884-5892

[20] Open Babel: An open chemical toolbox [J].

O'Boyle, Noel M. ;

Banck, Michael ;

James, Craig A. ;

Morley, Chris ;

Vandermeersch, Tim ;

Hutchison, Geoffrey R. .

JOURNAL OF CHEMINFORMATICS, 2011, 3

← 1 2 3 4 →