Web of Science: 29 citations, Scopus: 29 citations, Google Scholar: citations,
Increasing polarity in tacrine and huprine derivatives : potent anticholinesterase agents for the treatment of myasthenia gravis
Galdeano, Carles (Universitat de Barcelona. Laboratori de Química Farmacèutica)
Coquelle, Nicolas (Large-Scale Structures Group. Institut Laue-Langevin)
Cieslikiewicz-Bouet, Monika (Institut National des Sciences Appliquées-INSA (Rouen, França))
Bartolini, Manuela (Department of Pharmacy and Biotechnology. Alma Mater Studiorum University of Bologna)
Pérez, Belén (Universitat Autònoma de Barcelona. Institut de Neurociències)
Clos, Victòria (Universitat Autònoma de Barcelona. Institut de Neurociències)
Silman, Israel (Weizmann Institute of Science (Israel). Department of Neurobiology)
Jean, Ludovic (Institut National des Sciences Appliquées-INSA (Rouen, França))
Colletier, Jacques Phillippe (Université Grenoble Alpes. Institut de Biologie Structurale)
Renard, Pierre Yves (Institut National des Sciences Appliquées-INSA (Rouen, França))
Muñoz-Torrero López-Ibarra, Diego (Universitat de Barcelona. Laboratori de Química Farmacèutica)

Date: 2018
Abstract: Symptomatic treatment of myasthenia gravis is based on the use of peripherally-acting acetylcholinesterase (AChE) inhibitors that, in some cases, must be discontinued due to the occurrence of a number of side-effects. Thus, new AChE inhibitors are being developed and investigated for their potential use against this disease. Here, we have explored two alternative approaches to get access to peripherally-acting AChE inhibitors as new agents against myasthenia gravis, by structural modification of the brain permeable anti-Alzheimer AChE inhibitors tacrine, 6-chlorotacrine, and huprine Y. Both quaternization upon methylation of the quinoline nitrogen atom, and tethering of a triazole ring, with, in some cases, the additional incorporation of a polyphenol-like moiety, result in more polar compounds with higher inhibitory activity against human AChE (up to 190-fold) and butyrylcholinesterase (up to 40-fold) than pyridostigmine, the standard drug for symptomatic treatment of myasthenia gravis. The novel compounds are furthermore devoid of brain permeability, thereby emerging as interesting leads against myasthenia gravis.
Grants: Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR52
Ministerio de Economía y Competitividad SAF2014-57094-R
Note: Altres ajuts: FA/AAP-2013-65-101349
Note: Altres ajuts: ANR/ANR-12-BS07-0008-01
Note: Altres ajuts: ANR/ANR-11-LABX-0029
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Published in: Molecules, Vol. 23 Núm. 3 (2018) , p. 634, ISSN 1420-3049

DOI: 10.3390/molecules23030634
PMID: 29534488


19 p, 3.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2019-01-29, last modified 2024-01-16



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