Synthesis and Biological Evaluation of Novel Tacrine Derivatives and Tacrine-Coumarin Hybrids as Cholinesterase Inhibitors

被引：112

作者：

Hamulakova, Slavka ^{[1
]}

Janovec, Ladislav ^{[1
]}

Hrabinova, Martina ^{[2
]}

Spilovska, Katarina ^{[1
,4
]}

Korabecny, Jan ^{[3
,4
]}

Kristian, Pavol ^{[1
]}

Kuca, Kamil ^{[2
,3
]}

Imrich, Jan ^{[1
]}

机构：

[1] Safarik Univ, Fac Sci, Inst Chem, SK-04167 Kosice, Slovakia

[2] Univ Def, Fac Mil Hlth Sci, Ctr Adv Studies, CZ-50001 Hradec Kralove, Czech Republic

[3] Univ Hosp, Ctr Biomed Res, CZ-50005 Hradec Kralove, Czech Republic

[4] Univ Def, Fac Mil Hlth Sci, Dept Toxicol, CZ-50001 Hradec Kralove, Czech Republic

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 16期

关键词：

SITE ACETYLCHOLINESTERASE INHIBITORS; ALZHEIMERS-DISEASE; MULTIFUNCTIONAL AGENTS; AMYLOID AGGREGATION; TARGET; ANTIOXIDANT; CONGENERS; DESIGN; POTENT; THERAPY;

D O I：

10.1021/jm5008648

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel tacrine derivatives and tacrine coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine coumarin heterodimer 7c and tacrine derivative 6b were found to be the most potent inhibitors of human AChE (hAChE), demonstrating IC50 values of 0.0154 and 0.0263 mu M. Ligands 6b, 6c, and 7c exhibited the highest levels of inhibitory activity against human BuChE (hBuChE), demonstrating IC50 values that range from 0.228 to 0.328 mu M. Docking studies were performed in order to predict the binding modes of compounds 6b and 7c with hAChE/hBuChE.

引用

页码：7073 / 7084

页数：12

共 61 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]

AMES DJ, 1988, LANCET, V1, P887

[3] Effects of a tacrine-8-hydroxyquinoline hybrid (IQM-622) on Aβ accumulation and cell death: Involvement in hippocampal neuronal loss in Alzheimer's disease [J].

Antequera, Desiree ;

Bolos, Marta ;

Spuch, Carlos ;

Pascual, Consuelo ;

Ferrer, Isidro ;

Isabel Fernandez-Bachiller, Maria ;

Isabel Rodriguez-Franco, Maria ;

Carro, Eva .

NEUROBIOLOGY OF DISEASE, 2012, 46 (03) :682-691

[4] Tacrine-mefenamic acid hybrids for inhibition of acetylcholinesterase [J].

Bornstein, Joshua J. ;

Eckroat, Todd J. ;

Houghton, Jacob L. ;

Jones, Christopher K. ;

Green, Keith D. ;

Garneau-Tsodikova, Sylvie .

MEDCHEMCOMM, 2011, 2 (05) :406-412

[5] Tacrine based human cholinesterase inhibitors: Synthesis of peptidic-tethered derivatives and their effect on potency and selectivity [J].

Butini, Stefania ;

Guarino, Egeria ;

Campiani, Giuseppe ;

Brindisi, Margherita ;

Coccone, Salvatore Sanna ;

Fiorini, Isabella ;

Novellino, Ettore ;

Belinskaya, Tatyana ;

Saxena, Ashima ;

Gemma, Sandra .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (19) :5213-5216

[6] Synthesis and antimicrobial activity of some derivatives of (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide [J].

Cacic, M ;

Trkovnik, M ;

Cacic, F ;

Has-Schon, E .

MOLECULES, 2006, 11 (2-3) :134-147

[7] Peripheral and Dual Binding Site Acetylcholinesterase Inhibitors: Implications in treatment of Alzheimer's Disease [J].

Castro, Ana ;

Martinez, Ana .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2001, 1 (03) :267-272

[8] TACRINE [J].

DAVIS, KL ;

POWCHIK, P .

LANCET, 1995, 345 (8950) :625-630

[9] Cholinesterase inhibitors: a patent review (2007-2011) [J].

de los Rios, Cristobal .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2012, 22 (08) :853-869

[10]

El-Ansary Sohair L., 1992, Egyptian Journal of Pharmaceutical Sciences, V33, P379

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