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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/122306
Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis
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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.
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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. Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis. _Molecules_. 2018. Vol. 23(3), núm. 634. [consulta: 21 de gener de 2026]. ISSN: 1420-3049. [Disponible a: https://hdl.handle.net/2445/122306]