Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment

被引：58

作者：

Bachurin, Sergey O. ^{[1
]}

Shevtsova, Elena F. ^{[1
]}

Makhaeva, Galina F. ^{[1
]}

Grigoriev, Vladimir V. ^{[1
]}

Boltneva, Natalia P. ^{[1
]}

Kovaleva, Nadezhda V. ^{[1
]}

Lushchekina, Sofya V. ^{[1
,2
]}

Shevtsov, Pavel N. ^{[1
]}

Neganova, Margarita E. ^{[1
]}

Redkozubova, Olga M. ^{[1
]}

Bovina, Elena V. ^{[1
]}

Gabrelyan, Alexey V. ^{[1
]}

Fisenko, Vladimir P. ^{[3
]}

Sokolov, Vladimir B. ^{[1
]}

Aksinenko, Alexey Yu ^{[1
]}

Echeverria, Valentina ^{[4
]}

Barreto, George E. ^{[5
,6
]}

Aliev, Gjumrakch ^{[1
,7
,8
]}

机构：

[1] Russian Acad Sci, Inst Physiol Act Cpds, Chernogolovka 142432, Russia

[2] Russian Acad Sci, Emanuel Inst Biochem Phys, Moscow 119334, Russia

[3] IM Setchenov Moscow Med Acad, Therapeut Fac, Dept Pharmacol, Ul Bolshaya Pirogovskaya 2-6, Moscow 119881, Russia

[4] Univ San Sebastian, Gen Cruz 1577, Concepcion, Chile

[5] Pontificia Univ Javeriana, Fac Ciencias, Dept Nutr & Bioquim, Bogota, Colombia

[6] Univ Autonoma Chile, Inst Ciencias Biomed, Santiago, Chile

[7] GALLY Int Biomed Res Consulting LLC, San Antonio, TX 78229 USA

[8] Univ Atlanta, Sch Hlth Sci & Healthcare Adm, Johns Creek, GA 30097 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

俄罗斯科学基金会;

关键词：

METHYL-D-ASPARTATE; BETA-AMYLOID PEPTIDE; NMDA RECEPTOR ANTAGONISM; TARGET-DIRECTED LIGANDS; SLOW-BINDING INHIBITION; ALZHEIMERS-DISEASE; BUTYRYLCHOLINESTERASE INHIBITION; THERAPEUTIC TARGET; ESTERASE PROFILES; IFENPRODIL;

D O I：

10.1038/srep45627

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A new group of compounds, promising for the design of original multitarget therapeutic agents for treating neurodegenerative diseases, based on conjugates of aminoadamantane and carbazole derivatives was synthesized and investigated. Compounds of these series were found to interact with a group of targets that play an important role in the development of this type of diseases. First of all, these compounds selectively inhibit butyrylcholinest erase, block NMDA receptors containing NR2B subunits while maintaining the properties of MK-801 binding site blockers, exert microtubules stabilizing properties, and possess the ability to protect nerve cells from death at the calcium overload conditions. The leading compound C-2h has been shown the most promising effects on all analyzed parameters. Thus, these compounds can be regarded as promising candidates for the design of multitarget disease-modifying drugs for treatment of AD and/or similar neuropathologies.

引用

页数：15

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