Galdeano Cantador, CarlosCoquelle, NicolasCieslikiewicz-Bouet, MonikaBartolini, ManuelaPérez, BelénClos, VictòriaSilman, IsraelJean, LudovicColletier, Jacques-PhilippeRenard, Pierre-YvesMuñoz-Torrero López-Ibarra, Diego2018-05-112018-05-112018-03-111420-3049https://hdl.handle.net/2445/122306Symptomatic 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.19 p.application/pdfengcc-by (c) Galdeano Cantador, Carlos et al., 2018http://creativecommons.org/licenses/by/3.0/esAcetilcolinesterasaTriazolesMalalties neuromuscularsAcetylcholinesteraseTriazolesNeuromuscular diseasesinfo:eu-repo/semantics/article6792152018-05-11info:eu-repo/semantics/openAccess29534488