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dc.contributor.authorBautista-Aguilera, Óscar M.
dc.contributor.authorHagenow, Stefanie
dc.contributor.authorPalomino-Antolin, Alejandra
dc.contributor.authorFarré-Alins, Víctor
dc.contributor.authorIsmaili, Lhassane
dc.contributor.authorJoffrin, Pierre-Louis
dc.contributor.authorJimeno, María L.
dc.contributor.authorSoukup, Ondřej
dc.contributor.authorJanočková, Jana
dc.contributor.authorKalinowsky, Lena
dc.contributor.authorProschak, Ewgenij
dc.contributor.authorIriepa, Isabel
dc.contributor.authorMoraleda, Ignacio
dc.contributor.authorSchwed, Johannes S.
dc.contributor.authorRomero Martínez, Alejandro
dc.contributor.authorLópez-Muñoz, Francisco
dc.contributor.authorChioua, Mourad
dc.contributor.authorEgea, Javier
dc.contributor.authorRamsay, Rona R.
dc.contributor.authorMarco-Contelles, José
dc.contributor.authorStark, Holger
dc.date.accessioned2018-08-31T23:35:51Z
dc.date.available2018-08-31T23:35:51Z
dc.date.issued2017-09-27
dc.identifier.citationBautista-Aguilera , Ó M , Hagenow , S , Palomino-Antolin , A , Farré-Alins , V , Ismaili , L , Joffrin , P-L , Jimeno , M L , Soukup , O , Janočková , J , Kalinowsky , L , Proschak , E , Iriepa , I , Moraleda , I , Schwed , J S , Romero Martínez , A , López-Muñoz , F , Chioua , M , Egea , J , Ramsay , R R , Marco-Contelles , J & Stark , H 2017 , ' Multitarget-directed ligands combining cholinesterase and monoamine oxidase inhibition with histamine H 3 R antagonism for neurodegenerative diseases ' , Angewandte Chemie International Edition , vol. 56 , no. 41 , 201706072R2 , pp. 12765–12769 . https://doi.org/10.1002/anie.201706072en
dc.identifier.issn1433-7851
dc.identifier.otherPURE: 251083893
dc.identifier.otherPURE UUID: f4f5504d-7acc-4249-981b-044cc4a90c7d
dc.identifier.otherRIS: urn:258EFD58B516ADEDC49DD5E70B34BD45
dc.identifier.otherRIS: urn:258EFD58B516ADEDC49DD5E70B34BD45
dc.identifier.otherScopus: 85028598942
dc.identifier.otherORCID: /0000-0003-1535-4904/work/36874675
dc.identifier.otherWOS: 000411810600066
dc.identifier.urihttp://hdl.handle.net/10023/15938
dc.descriptionJ.M.C. thanks MINECO (SAF2012-33304 and SAF2015-65586-R). J.M.C., F.L.M., and A.R. thank UCJC for grants 2015-12, 2014-35, and 2015-21, respectively. J.E. thanks the Fondo de Investigaciones Sanitarias (FIS) (ISCIII/FEDER) (Programa Miguel Servet: CP14/00008 and PI16/00735) and Fundación Mutua Madrileña. O.S. and J.J. thank MHCZ-DRO (UHHK 00179906) for support. R.R.R., H.S., and J.M.C. acknowledge the EU COST Actions CM1103 and CM15135. E.P. and H.S. thank the German Research Foundation (DFG; PRO 1405/2-2, PRO 1405/4-1, SFB 1039 A07, and INST208/664-1).en
dc.description.abstractThe therapy of complex neurodegenerative diseases requires the development of multitarget-directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well as the histamine H3 receptor (H3R) were obtained by optimization of the neuroprotectant ASS234 by incorporating generally accepted H3R pharmacophore motifs. These small-molecule hits demonstrated balanced activities at the targets, mostly in the nanomolar concentration range. Additional in vitro studies showed antioxidative neuroprotective effects as well as the ability to penetrate the blood–brain barrier. With this promising in vitro profile, contilisant (at 1 mg kg−1 i.p.) also significantly improved lipopolysaccharide-induced cognitive deficits.
dc.format.extent5
dc.language.isoeng
dc.relation.ispartofAngewandte Chemie International Editionen
dc.rights© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1002/anie.201706072en
dc.subjectAntioxidantsen
dc.subjectDrug designen
dc.subjectInhibitorsen
dc.subjectMultitarget drugsen
dc.subjectNeurological agentsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectNDASen
dc.subjectBDCen
dc.subject.lccRC0321en
dc.subject.lccRMen
dc.titleMultitarget-directed ligands combining cholinesterase and monoamine oxidase inhibition with histamine H3R antagonism for neurodegenerative diseasesen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1002/anie.201706072
dc.description.statusPeer revieweden
dc.date.embargoedUntil2018-09-01


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