# name
Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis

# metadata.dc.description.abstract[].value
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.

# metadata.dc.rights[].value
cc-by (c) Galdeano Cantador, Carlos et al., 2018

# metadata.dc.source[].value
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

# metadata.dc.title[].value
Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis