Kazan (Volga region) Federal University, KFU
KAZAN
FEDERAL UNIVERSITY
 
6-METHYLURACIL DERIVATIVES AS BIFUNCTIONAL ACETYLCHOLINESTERASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
Form of presentationArticles in international journals and collections
Year of publication2015
Языканглийский
  • 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

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