Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178992
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dc.contributor.authorRiefolo, Fabio-
dc.contributor.authorSortino, Rosalba-
dc.contributor.authorMatera, Carlo-
dc.contributor.authorClaro Izaguirre, Enrique-
dc.contributor.authorPreda, Beatrice-
dc.contributor.authorVitiello, Simone-
dc.contributor.authorTraserra, Sara-
dc.contributor.authorJiménez, Marcel-
dc.contributor.authorGorostiza Langa, Pablo Ignacio-
dc.date.accessioned2021-07-12T09:45:16Z-
dc.date.available2022-06-23T05:10:20Z-
dc.date.issued2021-06-23-
dc.identifier.issn0022-2623-
dc.identifier.urihttp://hdl.handle.net/2445/178992-
dc.description.abstractTricyclic chemical structures are the core of many important drugs targeting all neurotransmitter pathways. These medicines enable effective therapies to treat from peptic ulcer disease to psychiatric disorders. However, when administered systemically, they cause serious adverse effects that limit their use. To obtain localized and on-demand pharmacological action using light, we have designed photoisomerizable ligands based on azobenzene that mimic the tricyclic chemical structure and display reversibly controlled activity. Pseudo-analogues of the tricyclic antagonist pirenzepine demonstrate that this is an effective strategy in muscarinic acetylcholine receptors, showing stronger inhibition upon illumination both in vitro and in cardiac atria ex vivo. Despite the applied chemical modifications to make pirenzepine derivatives sensitive to light stimuli, the most potent candidate of the set, cryptozepine-2, maintained a moderate but promising M1 vs M2 subtype selectivity. These photoswitchable “crypto-azologs” of tricyclic drugs might open a general way to spatiotemporally target their therapeutic action while reducing their systemic toxicity and adverse effects.ca
dc.format.extent63 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoengca
dc.publisherACS Publicationsca
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.1c00504-
dc.relation.ispartofJournal of Medicinal Chemistry, 2021, vol. 64, num.13, p. 9259-9270-
dc.relation.urihttps://doi.org/10.1021/acs.jmedchem.1c00504-
dc.rights(c) American Chemical Society, 2021-
dc.sourceArticles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))-
dc.subject.classificationMedicaments-
dc.subject.classificationNeurotransmissors-
dc.subject.classificationFotoquímica-
dc.subject.otherDrugs-
dc.subject.otherNeurotransmitters-
dc.subject.otherPhotochemistry-
dc.titleRational Design of Photochromic Analogues of Tricyclic Drugsca
dc.typeinfo:eu-repo/semantics/articleca
dc.typeinfo:eu-repo/semantics/acceptedVersion-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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