Maria Laura Bolognesi, Vincenza Andrisano, Manuela Bartolini, Andrea Cavalli, Anna Minarini, Maurizio Recanatini, Michela Rosini, Vincenzo Tumiatti, Carlo Melchiorre
{"title":"Heterocyclic inhibitors of AChE acylation and peripheral sites","authors":"Maria Laura Bolognesi, Vincenza Andrisano, Manuela Bartolini, Andrea Cavalli, Anna Minarini, Maurizio Recanatini, Michela Rosini, Vincenzo Tumiatti, Carlo Melchiorre","doi":"10.1016/j.farmac.2005.03.010","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><p><span><span>Notwithstanding the criticism to the so called “ cholinergic hypothesis”, the therapeutic strategies for the treatment of </span>Alzheimer's disease (AD) have been mainly centered on the restoration of cholinergic functionality and, until the last year, the only drugs licensed for the management of AD were the acetycholinesterase (AChE) inhibitors. Target enzyme AChE consists of a narrow gorge with two separate ligand binding sites: an acylation site at the bottom of the gorge containing the catalytic triad and a peripheral site located at the gorge rim, which encompasses binding sites for allosteric ligands. The aim of this short review is to update the knowledge on heterocyclic AChE inhibitors able to interact with the two sites of enzymes, structurally related to the well known inhibitors </span>physostigmine<span>, rivastigmine and propidium. The therapeutic potential of the dual site inhibithors in inhibiting amyloid-ß aggregatrion and deposition is also briefly summarised.</span></p></div>","PeriodicalId":77128,"journal":{"name":"Farmaco (Societa chimica italiana : 1989)","volume":"60 6","pages":"Pages 465-473"},"PeriodicalIF":0.0000,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.farmac.2005.03.010","citationCount":"22","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Farmaco (Societa chimica italiana : 1989)","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014827X05000698","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 22
Abstract
Notwithstanding the criticism to the so called “ cholinergic hypothesis”, the therapeutic strategies for the treatment of Alzheimer's disease (AD) have been mainly centered on the restoration of cholinergic functionality and, until the last year, the only drugs licensed for the management of AD were the acetycholinesterase (AChE) inhibitors. Target enzyme AChE consists of a narrow gorge with two separate ligand binding sites: an acylation site at the bottom of the gorge containing the catalytic triad and a peripheral site located at the gorge rim, which encompasses binding sites for allosteric ligands. The aim of this short review is to update the knowledge on heterocyclic AChE inhibitors able to interact with the two sites of enzymes, structurally related to the well known inhibitors physostigmine, rivastigmine and propidium. The therapeutic potential of the dual site inhibithors in inhibiting amyloid-ß aggregatrion and deposition is also briefly summarised.
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