Web of Science: 10 citations, Scopus: 10 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 (Laboratory COBRA (UMR 6014). Normandie Université. UNIROUEN. Institut National des Sciences Appliquées (INSA) Rouen. CNRS)
Bartolini, Manuela (Department of Pharmacy and Biotechnology. Alma Mater Studiorum University of Bologna)
Pérez, Belen (Universitat Autònoma de Barcelona. Institut de Neurociències)
Clos, Victòria (Universitat Autònoma de Barcelona. Institut de Neurociències)
Silman, Israel (Department of Neurobiology. Weizmann Institute of Science)
Jean, Ludovic (Laboratory COBRA (UMR 6014). Normandie Université. UNIROUEN. Institut National des Sciences Appliquées (INSA) Rouen. CNRS)
Colletier, Jacques Phillippe (Institut de Biologie Structurale. Université Grenoble Alpes. Centre National de la Recherche Scientifique (CNRS). Commissariat à l'Énergie Atomique (CEA) (UMR 5075))
Renard, Pierre Yves (Laboratory COBRA (UMR 6014). Normandie Université. UNIROUEN. Institut National des Sciences Appliquées (INSA) Rouen. CNRS)
Muñoz Torrero, 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.
Note: Número d'acord de subvenció FA/AAP-2013-65-101349
Note: Número d'acord de subvenció GC/AGAUR/2014SGR52
Note: Número d'acord de subvenció ANR/ANR-12-BS07-0008-01
Note: Número d'acord de subvenció ANR/ANR-11-LABX-0029
Note: Número d'acord de subvenció MINECO/SAF2014-57094-R
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 ; publishedVersion
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 (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2019-01-29, last modified 2021-01-08



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