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

被引：55

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

共 94 条

[1] Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease
Agis-Torres, Angel
Soellhuber, Monica
Fernandez, Maria
Sanchez-Montero, J. M.
[J]. CURRENT NEUROPHARMACOLOGY, 2014, 12 (01) : 2 - 36
[2] In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes
Al-Aboudi, Amal
Al-Qawasmeh, Raed A.
Shahwan, Alaa
Mahmood, Uzma
Khalid, Asaad
Ul-Haq, Zaheer
[J]. ACTA PHARMACOLOGICA SINICA, 2015, 36 (07) : 879 - 886
[3] 2018 Alzheimer's disease facts and figures
不详
[J]. ALZHEIMERS & DEMENTIA, 2018, 14 (03) : 367 - 425
[4] Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents
Averina, Elena B.
Vasilenko, Dmitry A.
Gracheva, Yulia A.
Grishin, Yuri K.
Radchenko, Eugene V.
Burmistrov, Vladimir V.
Butov, Gennady M.
Neganova, Margarita E.
Serkova, Tatyana P.
Redkozubova, Olga M.
Shevtsova, Elena F.
Milaeva, Elena R.
Kuznetsova, Tamara S.
Zefirov, Nikolay S.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2016, 24 (04) : 712 - 720
[5] Bachurin S. O., 2015, Russian Federation patent Appl., Patent No. 2015146079
[6] Bachurin S. O, 2015, Russian Fedeartion patent Appl, Patent No. 2015146080
[7] Drugs in Clinical Trials for Alzheimer's Disease: The Major Trends
Bachurin, Sergey O.
Bovina, Elena V.
Ustyugov, Aleksey A.
[J]. MEDICINAL RESEARCH REVIEWS, 2017, 37 (05) : 1186 - 1225
[8] Microtubule Stabilizing Agents as Potential Treatment for Alzheimer's Disease and Related Neurodegenerative Tauopathies
Ballatore, Carlo
Brunden, Kurt R.
Huryn, Donna M.
Trojanowski, John Q.
Lee, Virginia M. -Y.
Smith, Amos B., III
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (21) : 8979 - 8996
[9] The Glutamate Hypothesis in ALS: Pathophysiology and Drug Development
Blasco, H.
Mavel, S.
Corcia, P.
Gordon, P. H.
[J]. CURRENT MEDICINAL CHEMISTRY, 2014, 21 (31) : 3551 - 3575
[10] Multitarget Drug Discovery and Polypharmacology
Bolognesi, Maria Laura
Cavalli, Andrea
[J]. CHEMMEDCHEM, 2016, 11 (12) : 1190 - 1192

← 1 2 3 4 5 6 7 8 9 10 →