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https://hdl.handle.net/2445/122306
Title: | Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis |
Author: | Galdeano Cantador, Carlos Coquelle, Nicolas Cieslikiewicz-Bouet, Monika Bartolini, Manuela Pérez, Belén Clos, Victòria Silman, Israel Jean, Ludovic Colletier, Jacques-Philippe Renard, Pierre-Yves Muñoz-Torrero López-Ibarra, Diego |
Keywords: | Acetilcolinesterasa Triazoles Malalties neuromusculars Acetylcholinesterase Triazoles Neuromuscular diseases |
Issue Date: | 11-Mar-2018 |
Publisher: | MDPI |
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: | Reproducció del document publicat a: https://doi.org/10.3390/molecules23030634 |
It is part of: | Molecules, 2018, vol. 23(3), num. 634 |
URI: | https://hdl.handle.net/2445/122306 |
Related resource: | https://doi.org/10.3390/molecules23030634 |
ISSN: | 1420-3049 |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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