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dc.contributor.authorSola, I.
dc.contributor.authorCastellà, S.
dc.contributor.authorViayna, E.
dc.contributor.authorGaldeano, C.
dc.contributor.authorTaylor, M.C.
dc.contributor.authorGbedema, Stephen Y.
dc.contributor.authorPérez, B.
dc.contributor.authorClos, M.V.
dc.contributor.authorJones, D.C.
dc.contributor.authorFairlamb, A.H.
dc.contributor.authorWright, Colin W.
dc.contributor.authorKelly, J.M.
dc.contributor.authorMuñoz-Torrero, D.
dc.date.accessioned2015-11-24T16:55:14Z
dc.date.available2015-11-24T16:55:14Z
dc.date.issued2015-08
dc.identifier.citationSola I, Castella S, Viayna E et al (2015) Synthesis, biological profiling and mechanistic studies of 4-amonoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity. Bioorganic and Medicinal Chemistry. 23(16): 5156-5167.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7485
dc.descriptionYesen_US
dc.description.abstractDual submicromolar trypanocidal–antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.bmc.2015.01.031en_US
dc.rights© 2015 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMolecular hybridization; Trypanocidal agents; Antimalarial agents; Trypanothione reductase inhibitors; Inhibitors of β-haematin formation; Brain permeabilityen_US
dc.titleSynthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity.en_US
dc.status.refereedyesen_US
dc.date.application2015-01-24
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-07-25T12:09:31Z


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