{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:30:38Z","timestamp":1771824638039,"version":"3.50.1"},"reference-count":89,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Pesquisa e Amparo do Estado de S\u00e3o Paulo-FAPESP","award":["12\/04054-5"],"award-info":[{"award-number":["12\/04054-5"]}]},{"name":"Funda\u00e7\u00e3o de Pesquisa e Amparo do Estado de S\u00e3o Paulo-FAPESP","award":["12\/14114-5"],"award-info":[{"award-number":["12\/14114-5"]}]},{"name":"Funda\u00e7\u00e3o de Pesquisa e Amparo do Estado de S\u00e3o Paulo-FAPESP","award":["13\/50788-3"],"award-info":[{"award-number":["13\/50788-3"]}]},{"name":"Funda\u00e7\u00e3o de Pesquisa e Amparo do Estado de S\u00e3o Paulo-FAPESP","award":["14-10414-0"],"award-info":[{"award-number":["14-10414-0"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"CSIC","doi-asserted-by":"publisher","award":["i-LINK-0801"],"award-info":[{"award-number":["i-LINK-0801"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO","doi-asserted-by":"publisher","award":["SAF2016-76693-R"],"award-info":[{"award-number":["SAF2016-76693-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"MINECO","doi-asserted-by":"publisher","award":["CTQ2015-64597-C2-1"],"award-info":[{"award-number":["CTQ2015-64597-C2-1"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MEC","award":["FPU15\/1465"],"award-info":[{"award-number":["FPU15\/1465"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2017,10]]},"DOI":"10.1016\/j.ejmech.2017.08.051","type":"journal-article","created":{"date-parts":[[2017,8,27]],"date-time":"2017-08-27T00:01:09Z","timestamp":1503792069000},"page":"773-791","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":51,"special_numbering":"C","title":["From dual binding site acetylcholinesterase inhibitors to allosteric modulators: A new avenue for disease-modifying drugs in Alzheimer's disease"],"prefix":"10.1016","volume":"139","author":[{"given":"Talita P.C.","family":"Chierrito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susimaire","family":"Pedersoli-Mantoani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Roca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Requena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Sebastian-Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willian O.","family":"Castillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia C.S.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concepci\u00f3n","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elza T.","family":"Sakamoto-Hojo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catarina S.","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Jim\u00e9nez-Barbero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Javier","family":"Ca\u00f1ada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria E.","family":"Campillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2707-8110","authenticated-orcid":false,"given":"Ana","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivone","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2017.08.051_bib1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.31887\/DCNS.2003.5.1\/hhippius","article-title":"The discovery of Alzheimer's disease","volume":"5","author":"Hippius","year":"2003","journal-title":"Dialogues Clin. Neurosci."},{"key":"10.1016\/j.ejmech.2017.08.051_bib2","unstructured":"Alzheimer Society: https:\/\/www.alzheimers.org.uk\/. (10.12.2015)."},{"key":"10.1016\/j.ejmech.2017.08.051_bib3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.arcmed.2012.11.008","article-title":"Alzheimer's disease: critical notes on the history of a medical concept","volume":"43","author":"Ramirez-Bermudez","year":"2012","journal-title":"Arch. Med. Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib4","unstructured":"https:\/\/www.alz.co.uk\/research\/worldalzheimerreport2016sheet. (09.01.2017)."},{"key":"10.1016\/j.ejmech.2017.08.051_bib5","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0011-393X(03)00059-6","article-title":"Cholinesterase inhibitors for the treatment of Alzheimer's disease","volume":"64","author":"Grossberg","year":"2003","journal-title":"Curr. Ther. Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/13543784.15.1.1","article-title":"Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease","volume":"15","author":"Martinez","year":"2006","journal-title":"Expert Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2017.08.051_bib7","first-page":"641","article-title":"Current approaches against Alzheimer's disease in clinical trials","volume":"27","author":"Kuca","year":"2016","journal-title":"J.\u00a0Braz. Chem. Soc."},{"key":"10.1016\/j.ejmech.2017.08.051_bib8","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1080\/15216540701283882","article-title":"Soluble protein oligomers as emerging toxins in alzheimer's and other amyloid diseases","volume":"59","author":"Ferreira","year":"2007","journal-title":"IUBMB Life"},{"key":"10.1016\/j.ejmech.2017.08.051_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aad9704","article-title":"The BACE1 inhibitor verubecestat (MK-8931) reduces CNS \u03b2-amyloid in animal models and in Alzheimer's disease patients","volume":"8","author":"Kennedy","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejmech.2017.08.051_bib10","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.2174\/1567205013666160819124206","article-title":"The anti-inflammatory role of minocycline in Alzheimer's disease","volume":"13","author":"Budni","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib11","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1586\/14737175.2016.1140039","article-title":"Tau-directed approaches for the treatment of Alzheimer's disease: focus on leuco-methylthioninium","volume":"16","author":"Seripa","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"10.1016\/j.ejmech.2017.08.051_bib12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40478-015-0204-4","article-title":"Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau","volume":"3","author":"Hochgr\u00e4fe","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.ejmech.2017.08.051_bib13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/14728214.2016.1241232","article-title":"Emerging drugs to reduce abnormal \u03b2-amyloid protein in Alzheimer's disease patients","volume":"21","author":"Panza","year":"2016","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"10.1016\/j.ejmech.2017.08.051_bib14","unstructured":"http:\/\/www.alzforum.org\/news\/conference-coverage\/clinical-trials-alzheimers-disease. (11.01.2017)."},{"key":"10.1016\/j.ejmech.2017.08.051_bib15","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1074\/jbc.M507892200","article-title":"Temporal profile of amyloid-beta (Abeta) oligomerization in an in\u00a0vivo model of Alzheimer disease. A link between Abeta and tau pathology","volume":"281","author":"Oddo","year":"2006","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib16","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.bbadis.2013.09.015","article-title":"Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics studies","volume":"1842","author":"Swomley","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"10.1016\/j.ejmech.2017.08.051_bib17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1089\/ars.2012.5027","article-title":"Amyloid \u03b2-peptide (1\u201342)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression","volume":"19","author":"Butterfield","year":"2013","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejmech.2017.08.051_bib18","doi-asserted-by":"crossref","first-page":"825.e1","DOI":"10.1016\/j.neurobiolaging.2011.05.003","article-title":"Different \u03b2-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity","volume":"33","author":"Bao","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.ejmech.2017.08.051_bib19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.pneurobio.2016.06.004","article-title":"Alzheimer's disease due to loss of function: a new synthesis of the available data","volume":"143","author":"Kepp","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.ejmech.2017.08.051_bib20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.1742-4658.2007.06238.x","article-title":"Amyloid-cholinesterase interactions. Implications for Alzheimer's disease","volume":"275","author":"Inestrosa","year":"2008","journal-title":"FEBS J."},{"key":"10.1016\/j.ejmech.2017.08.051_bib21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.arr.2014.03.008","article-title":"Alzheimer's disease, enzyme targets and drug discovery struggles: from natural products to drug prototypes","volume":"15","author":"Silva","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ejmech.2017.08.051_bib22","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1021\/jm8001313","article-title":"Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced \u03b2-amyloid aggregation","volume":"51","author":"Camps","year":"2008","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib23","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.1021\/jm0503289","article-title":"Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase Inhibitors:\u2009 new disease-modifying agents for Alzheimer's disease","volume":"48","author":"Mu\u00f1oz-Ruiz","year":"2005","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib24","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1021\/jm200840c","article-title":"Huprine\u2013tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases","volume":"55","author":"Galdeano","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib25","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/cmdc.201000086","article-title":"Bis(7)-tacrine derivatives as multitarget-directed ligands: focus on anticholinesterase and antiamyloid activities","volume":"5","author":"Bolognesi","year":"2010","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2017.08.051_bib26","doi-asserted-by":"crossref","first-page":"10282","DOI":"10.1021\/jm300871x","article-title":"Structures of human acetylcholinesterase in complex with pharmacologically important ligands","volume":"55","author":"Cheung","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ejmech.2017.02.045","article-title":"Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors","volume":"133","author":"Lan","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib28","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.ejmech.2016.09.057","article-title":"Design, synthesis, in-silico and biological evaluation of novel donepezil derivatives as multi-target-directed ligands for the treatment of Alzheimer's disease","volume":"125","author":"Mishra","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib29","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ejmech.2016.05.055","article-title":"New cinnamic \u2013 N-benzylpiperidine and cinnamic \u2013 N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties","volume":"121","author":"Estrada","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib30","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.ejmech.2017.02.043","article-title":"Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease","volume":"130","author":"Dias","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib31","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ejmech.2014.04.078","article-title":"Donepezil\u00a0+\u00a0propargylamine\u00a0+\u00a08-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer's disease","volume":"80","author":"Wang","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.cbi.2010.02.013","article-title":"Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates","volume":"187","author":"Camps","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.ejmech.2017.08.051_bib33","doi-asserted-by":"crossref","first-page":"6588","DOI":"10.1016\/j.bmc.2005.09.029","article-title":"Donepezil\u2013tacrine hybrid related derivatives as new dual binding site inhibitors of AChE","volume":"13","author":"Alonso","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib34","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1016\/j.bmcl.2004.07.005","article-title":"Synthesis and evaluation of tacrine\u2013E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease","volume":"14","author":"Shao","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2017.08.051_bib35","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ejmech.2014.05.066","article-title":"7-MEOTA\u2013donepezil like compounds as cholinesterase inhibitors: synthesis, pharmacological evaluation, molecular modeling and QSAR studies","volume":"82","author":"Korabecny","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mrfmmm.2007.03.014","article-title":"Genotoxicity of non-covalent interactions: DNA intercalators","volume":"623","author":"Ferguson","year":"2007","journal-title":"Mutat. Res.\/Fund. Mol. Mech. Mutagen."},{"key":"10.1016\/j.ejmech.2017.08.051_bib37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0027-5107(95)00206-5","article-title":"Mutagenicity of acridines in a reversion assay based on tetracycline resistance in plasmid pBR322 in Escherichia coli","volume":"351","author":"Hoffmann","year":"1996","journal-title":"Mutat. Res.\/Fund. Mol. Mech. Mutagen."},{"key":"10.1016\/j.ejmech.2017.08.051_bib38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2174\/138920008784220619","article-title":"Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease","volume":"9","author":"Patocka","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.ejmech.2017.08.051_bib39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsps.2012.03.002","article-title":"Quinoline: a versatile heterocyclic","volume":"21","author":"Marella","year":"2013","journal-title":"Saudi Pharm. J."},{"key":"10.1016\/j.ejmech.2017.08.051_bib40","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ejmech.2016.07.052","article-title":"Rational modification of donepezil as multifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer's disease","volume":"123","author":"Wang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib41","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jmgm.2005.12.002","article-title":"Molecular modeling, docking and ADMET studies applied to the design of a novel hybrid for treatment of Alzheimer's disease","volume":"25","author":"da Silva","year":"2006","journal-title":"J.\u00a0Mol. Graph. Model."},{"key":"10.1016\/j.ejmech.2017.08.051_bib42","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1016\/S0040-4039(00)97905-X","article-title":"Reductive amination of aldehydes and ketones by using sodium triacetoxyborohydride","volume":"31","author":"Abdel-Magid","year":"1990","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2017.08.051_bib43","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1002\/ejoc.200800363","article-title":"Synthesis of \u03b1,\u03b1-difluoro-\u03b2-amino esters or gem-difluoro-\u03b2-lactams as potential metallocarboxypeptidase inhibitors","volume":"2008","author":"Boyer","year":"2008","journal-title":"Eur. J. Org. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib44","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1016\/j.bmc.2010.06.071","article-title":"Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R)","volume":"18","author":"Engen","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib45","first-page":"5","article-title":"Improved oxidation of active methyl group of N-heteroaromatic compounds by selenium dioxide in the presence of tert-butyl hydroperoxide","volume":"60","author":"Tagawa","year":"2003","journal-title":"Heterocycles"},{"key":"10.1016\/j.ejmech.2017.08.051_bib46","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1021\/jo00170a070","article-title":"Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones","volume":"48","author":"Dess","year":"1983","journal-title":"J.\u00a0Org. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib47","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1016\/j.bmc.2010.02.053","article-title":"\u2018Click chemistry\u2019 synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase","volume":"18","author":"Carvalho","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib48","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.1021\/jo0600095","article-title":"Highly diastereoselective one-pot synthesis of spiro{cyclopenta[a]indene-2,2\u2032-indene}diones from 1-indanones and aromatic aldehydes","volume":"71","author":"Camps","year":"2006","journal-title":"J.\u00a0Org. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/(SICI)1097-458X(200004)38:4<265::AID-MRC637>3.0.CO;2-#","article-title":"One- and two-dimensional gradient-selected HSQMBC NMR experiments for the efficient analysis of long-range heteronuclear coupling constants","volume":"38","author":"Williamson","year":"2000","journal-title":"Magn. Reson. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/mrc.1723","article-title":"Long-range JCH heteronuclear coupling constants in cyclopentane derivatives","volume":"44","author":"Lacerda","year":"2006","journal-title":"Magn. Reson. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib51","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/mrc.1912","article-title":"Long-range JCH heteronuclear coupling constants in cyclopentane derivatives. Part II","volume":"45","author":"Lacerda","year":"2007","journal-title":"Magn. Reson. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib52","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/mrc.2182","article-title":"Stereochemistry of cyclopentane derivatives from 2, 3JCH dependence on dihedral angle (\u03b8 H C C X)","volume":"46","author":"Lacerda","year":"2008","journal-title":"Magn. Reson. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib53","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1039\/b801592a","article-title":"Stereochemistry of 1,2-elimination reactions at the E2-E1cB interface-tert-butyl 3-tosyloxybutanoate and its thioester","volume":"6","author":"Mohrig","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib54","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1002\/ejoc.200501005","article-title":"The first centrohexaindane bearing twelve functional groups at its outer molecular periphery and related lower veratrole-derived centropolyindanes","volume":"2006","author":"Harig","year":"2006","journal-title":"Eur. J. Org. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib55","doi-asserted-by":"crossref","first-page":"16760","DOI":"10.1002\/chem.201302453","article-title":"BippyPhos: a single ligand with unprecedented scope in the Buchwald-Hartwig amination of (hetero)aryl chlorides","volume":"19","author":"Crawford","year":"2013","journal-title":"Chemistry"},{"key":"10.1016\/j.ejmech.2017.08.051_bib56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A\u00a0new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2017.08.051_bib57","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/anie.200390233","article-title":"NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors","volume":"42","author":"Meyer","year":"2003","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2017.08.051_bib58","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/mrc.1381","article-title":"Competition STD NMR for the detection of high-affinity ligands and NMR-based screening","volume":"42","author":"Wang","year":"2004","journal-title":"Magn. Reson Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib59","doi-asserted-by":"crossref","first-page":"6641","DOI":"10.1002\/chem.201203966","article-title":"Molecular recognition of rosmarinic acid from Salvia sclareoides extracts by acetylcholinesterase: a new binding site detected by NMR spectroscopy","volume":"19","author":"Marcelo","year":"2013","journal-title":"Chemistry"},{"key":"10.1016\/j.ejmech.2017.08.051_bib60","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/asia.201201063","article-title":"Natural compounds against Alzheimer's disease: molecular recognition of Abeta1-42 peptide by Salvia sclareoides extract and its major component, rosmarinic acid, as investigated by NMR","volume":"8","author":"Airoldi","year":"2013","journal-title":"Chem. Asian J."},{"key":"10.1016\/j.ejmech.2017.08.051_bib61","doi-asserted-by":"crossref","first-page":"8555","DOI":"10.1021\/jm201090k","article-title":"Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR","volume":"54","author":"Viegas","year":"2011","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib62","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1021\/ct0501811","article-title":"PELE:\u2009 protein energy landscape exploration. A novel Monte Carlo based technique","volume":"1","author":"Borrelli","year":"2005","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2017.08.051_bib63","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib64","unstructured":"Roca C., Requena C., Sebastian V., Malhora S., P\u00e9rez C., Martinez A., P\u00e1ez J.A. and Campillo, N.E.. AChE, an old well-known enzyme with new allosteric sites: discovery of allosteric modulators, J. Chem. Inf. Mol. Model., (submitted for publication)."},{"key":"10.1016\/j.ejmech.2017.08.051_bib65","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.ejmech.2017.08.051_bib66","doi-asserted-by":"crossref","first-page":"e0121092","DOI":"10.1371\/journal.pone.0121092","article-title":"A\u00a0wrench in the works of human acetylcholinesterase: soman induced conformational changes revealed by molecular dynamics simulations","volume":"10","author":"Bennion","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2017.08.051_bib67","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/prot.25073","article-title":"Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface","volume":"84","author":"Franklin","year":"2016","journal-title":"Proteins"},{"key":"10.1016\/j.ejmech.2017.08.051_bib68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmb.2008.02.034","article-title":"Allostery: absence of a change in shape does not imply that allostery is not at play","volume":"378","author":"Tsai","year":"2008","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2017.08.051_bib69","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.brainres.2010.03.102","article-title":"Comparison between proliferative and neuron-like SH-SY5Y cells as an in\u00a0vitro model for Parkinson disease studies","volume":"1337","author":"Lopes","year":"2010","journal-title":"Brain Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib70","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/bph.12359","article-title":"Neuronal AChE splice variants and their non-hydrolytic functions: redefining a target of AChE inhibitors?","volume":"170","author":"Zimmermann","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2017.08.051_bib71","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.cbi.2013.03.015","volume":"203","author":"Greenfield","year":"2013","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.ejmech.2017.08.051_bib72","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/BJ20071404","article-title":"Interaction of acetylcholinesterase with the G4 domain of the laminin \u03b11-chain","volume":"411","author":"Johnson","year":"2008","journal-title":"Biochem. J."},{"key":"10.1016\/j.ejmech.2017.08.051_bib73","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s12640-016-9699-0","article-title":"Differentiation enhances dopaminergic features, changes redox parameters, and increases dopamine transporter dependency in 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells","volume":"31","author":"Lopes","year":"2017","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.ejmech.2017.08.051_bib74","doi-asserted-by":"crossref","DOI":"10.1007\/s12035-016-0189-4","article-title":"Changes in cell cycle and up-regulation of neuronal markers during SH-SY5Y neurodifferentiation by retinoic acid are mediated by reactive species production and oxidative stress","author":"Kunzler","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.ejmech.2017.08.051_bib75","series-title":"Schr\u00f6dinger Release 2016-1: Schr\u00f6dinger Suite 2016-1 Protein Preparation Wizard","year":"2016"},{"key":"10.1016\/j.ejmech.2017.08.051_bib76","series-title":"AMBER 12","author":"Case","year":"2012"},{"key":"10.1016\/j.ejmech.2017.08.051_bib77","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2017.08.051_bib78","unstructured":"Gaussian 09, R. A. M. J. F., G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman, and D. J. Fox, Gaussian, Inc., Wallingford CT, 2016. 2016."},{"key":"10.1016\/j.ejmech.2017.08.051_bib79","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J.\u00a0Chem. Phys."},{"key":"10.1016\/j.ejmech.2017.08.051_bib80","doi-asserted-by":"crossref","first-page":"046101","DOI":"10.1063\/1.2431176","article-title":"A\u00a0common, avoidable source of error in molecular dynamics integrators","volume":"126","author":"Lippert","year":"2007","journal-title":"J.\u00a0Chem. Phys."},{"key":"10.1016\/j.ejmech.2017.08.051_bib81","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J.\u00a0Chem. Phys."},{"key":"10.1016\/j.ejmech.2017.08.051_bib82","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J.\u00a0Chem. Theory Comput."},{"key":"10.1016\/j.ejmech.2017.08.051_bib83","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J.\u00a0Mol. Graph."},{"key":"10.1016\/j.ejmech.2017.08.051_bib84","series-title":"XMGRACE","author":"PJ","year":"2005"},{"key":"10.1016\/j.ejmech.2017.08.051_bib85","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1021\/ci4000294","article-title":"TRAPP: a tool for analysis of transient binding pockets in proteins","volume":"53","author":"Kokh","year":"2013","journal-title":"J.\u00a0Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2017.08.051_bib86","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.nbd.2005.02.003","article-title":"Trehalose differentially inhibits aggregation and neurotoxicity of beta-amyloid 40 and 42","volume":"20","author":"Liu","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.ejmech.2017.08.051_bib87","doi-asserted-by":"crossref","first-page":"259765","DOI":"10.1155\/2014\/259765","article-title":"Assessment of cellular responses after short- and long-term exposure to silver nanoparticles in human neuroblastoma (SH-SY5Y) and astrocytoma (D384) cells","volume":"2014","author":"Coccini","year":"2014","journal-title":"Sci. World J."},{"key":"10.1016\/j.ejmech.2017.08.051_bib88","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.neuro.2016.10.013","article-title":"Galanthamine decreases genotoxicity and cell death induced by beta-amyloid peptide in SH-SY5Y cell line","volume":"57","author":"Castillo","year":"2016","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.ejmech.2017.08.051_bib89","doi-asserted-by":"crossref","first-page":"7637","DOI":"10.3892\/mmr.2015.4397","article-title":"Tenuifoliside A promotes neurite outgrowth in PC12 cells via the PI3K\/AKT and MEK\/ERK\/CREB signaling pathways","volume":"12","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523417306621?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523417306621?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T20:31:13Z","timestamp":1659385873000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523417306621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":89,"alternative-id":["S0223523417306621"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2017.08.051","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"From dual binding site acetylcholinesterase inhibitors to allosteric modulators: A new avenue for disease-modifying drugs in Alzheimer's disease","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"http:\/\/dx.doi.org\/10.1016\/j.ejmech.2017.08.051","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}