Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S10013 secretion and a molecular modeling approach

被引：39

作者：

Ceschi, Marco Antonio ^{[1
]}

da Costa, Jessie Sobieski ^{[1
]}

Bizarro Lopes, Joao Paulo ^{[1
]}

Camara, Viktor Saraiva ^{[1
]}

Campo, Leandra Franciscato ^{[1
]}

de Amorim Borges, Antonio Cesar ^{[1
]}

Saraiva Goncalves, Carlos Alberto ^{[2
]}

de Souza, Daniela Fraga ^{[2
]}

Konrath, Eduardo Luis ^{[3
]}

Martins Karl, Ana Luiza ^{[4
]}

Guedes, Isabella Alvim ^{[4
]}

Dardenne, Laurent Emmanuel ^{[4
]}

机构：

[1] Univ Fed Rio Grande do Sul, Inst Quim, Ave Bento Goncalves 9500,Campus Vale, BR-91501970 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Dept Quim, Rua Ramiro Barcelos 2600, BR-90035003 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Fac Farm, Ave Ipiranga 2752, BR-90610000 Porto Alegre, RS, Brazil

[4] LNCC, Ave Getulio Vargas 333, BR-25651075 Petropolis, RJ, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 121卷

关键词：

Tacrine; Tianeptine; AChE; BuChE; SlOOB secretion; Coupling reaction; Molecular modeling; SITE ACETYLCHOLINESTERASE INHIBITORS; ALZHEIMERS-DISEASE; BIOLOGICAL EVALUATION; CHOLINERGIC HYPOTHESIS; THERAPEUTIC TARGET; ACCURATE DOCKING; HIGHLY POTENT; BINDING; DESIGN; BUTYRYLCHOLINESTERASE;

D O I：

10.1016/j.ejmech.2016.06.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC center dot HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：758 / 772

页数：15

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