KFU. Card publication. 6-methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease

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FEDERAL UNIVERSITY

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6-METHYLURACIL DERIVATIVES AS BIFUNCTIONAL ACETYLCHOLINESTERASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

Form of presentation

Articles in international journals and collections

Year of publication

2015

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Authors, employees of KFU

Zobov Vladimir Vasilevich, author

Masson Patrik Ivon Moris , author

Nikolskiy Evgeniy Evgenevich, author

Petrov Aleksandr Aleksandrovich, author

Petrov Konstantin Aleksandrovich, author

Bibliographic description in the original language

Semenov V.E. 6-methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease / V.E. Semenov, I.V. Zueva, M.A. Mukhamedyarov, S.V. Lushchekina, A.D. Kharlamova, E.O. Petukhova, A.S. Mikhailov, S.N. Podyachev, L.F. Saifina, K.A. Petrov, O.A. Minnekhanova, V.V. Zobov, E.E. Nikolsky, P. Masson, V.S. Reznik // ChemMedChem, Volume 10, Issue 11, 1 November 2015, Pages 1863-1874

Annotation

Novel 6-methyluracil derivatives with ω-(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron-withdrawing substituents on the benzyl rings. The compounds are mixed-type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10 000-fold higher than that for human butyrylcholinesterase (hBuChE). In our efforts to identify compounds to treat Alzheimer′s disease, we found that 1,3-bis[ω-(substituted benzylethylamino)alkyl]-6-methyluracils bind to the active site gorge and peripheral anionic site of acetylcholinesterase (AChE). These compounds can cross the blood-brain barrier, and decrease the number and area of β-amyloid plaques in the brain.

Keywords

6-methyluracil; acetylcholinesterase; Alzheimer's disease; molecular modeling; reversible inhibitors

The name of the journal

ChemMedChem

URL

http://www.scopus.com/inward/record.url?eid=2-s2.0-84946040911&partnerID=40&md5=39284f30f69f2f3e7eeef9d25581f115

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=136029&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Zobov Vladimir Vasilevich	ru_RU
dc.contributor.author	Masson Patrik Ivon Moris	ru_RU
dc.contributor.author	Nikolskiy Evgeniy Evgenevich	ru_RU
dc.contributor.author	Petrov Aleksandr Aleksandrovich	ru_RU
dc.contributor.author	Petrov Konstantin Aleksandrovich	ru_RU
dc.date.accessioned	2015-01-01T00:00:00Z	ru_RU
dc.date.available	2015-01-01T00:00:00Z	ru_RU
dc.date.issued	2015	ru_RU
dc.identifier.citation	Semenov V.E. 6-methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease / V.E. Semenov, I.V. Zueva, M.A. Mukhamedyarov, S.V. Lushchekina, A.D. Kharlamova, E.O. Petukhova, A.S. Mikhailov, S.N. Podyachev, L.F. Saifina, K.A. Petrov, O.A. Minnekhanova, V.V. Zobov, E.E. Nikolsky, P. Masson, V.S. Reznik // ChemMedChem, Volume 10, Issue 11, 1 November 2015, Pages 1863-1874	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=136029&p_lang=2	ru_RU
dc.description.abstract	ChemMedChem	ru_RU
dc.description.abstract	Novel 6-methyluracil derivatives with ω-(substituted benzylethylamino)alkyl chains at the nitrogen atoms of the pyrimidine ring were designed and synthesized. The numbers of methylene groups in the alkyl chains were varied along with the electron-withdrawing substituents on the benzyl rings. The compounds are mixed-type reversible inhibitors of cholinesterases, and some of them show remarkable selectivity for human acetylcholinesterase (hAChE), with inhibitory potency in the nanomolar range, more than 10 000-fold higher than that for human butyrylcholinesterase (hBuChE). In our efforts to identify compounds to treat Alzheimer′s disease, we found that 1,3-bis[ω-(substituted benzylethylamino)alkyl]-6-methyluracils bind to the active site gorge and peripheral anionic site of acetylcholinesterase (AChE). These compounds can cross the blood-brain barrier, and decrease the number and area of β-amyloid plaques in the brain.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	6-methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease	ru_RU
dc.type	Articles in international journals and collections	ru_RU