Galdeano_2018_Molecules_23_

Reference

Title : Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis - Galdeano_2018_Molecules_23_
Author(s) : Galdeano C , Coquelle N , Cieslikiewicz-Bouet M , Bartolini M , Perez B , Clos MV , Silman I , Jean L , Colletier JP , Renard PY , Munoz-Torrero D
Ref : Molecules , 23 : , 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.
ESTHER : Galdeano_2018_Molecules_23_
PubMedSearch : Galdeano_2018_Molecules_23_
PubMedID: 29534488
Gene_locus related to this paper: torca-ACHE

Related information

Gene_locus related to this paper: torca-ACHE

Citations formats

Galdeano C, Coquelle N, Cieslikiewicz-Bouet M, Bartolini M, Perez B, Clos MV, Silman I, Jean L, Colletier JP, Renard PY, Munoz-Torrero D (2018)
Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis
Molecules 23 :

Galdeano C, Coquelle N, Cieslikiewicz-Bouet M, Bartolini M, Perez B, Clos MV, Silman I, Jean L, Colletier JP, Renard PY, Munoz-Torrero D (2018)
Molecules 23 :