First Report on Cationic Triphenylphosphonium Compounds as Mitochondriotropic H3R Ligands with Antioxidant Properties

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dc.article.number1345
dc.catalogadoraba
dc.contributor.authorWerner T.
dc.contributor.authorAñazco Martínez, Tito Alonso
dc.contributor.authorOsses-Mendoza P.
dc.contributor.authorCastro-Alvarez A.
dc.contributor.authorSalas Sánchez, Cristián Osvaldo
dc.contributor.authorBridi R.
dc.contributor.authorStark H.
dc.contributor.authorEspinosa Bustos, Christian Marcelo
dc.date.accessioned2025-04-01T13:15:53Z
dc.date.available2025-04-01T13:15:53Z
dc.date.issued2024
dc.description.abstractNeurodegenerative diseases are a major public health problem due to the aging population and multifaceted pathology; therefore, the search for new therapeutic alternatives is of the utmost importance. In this sense, a series of six 1-(3-phenoxypropyl)piperidines alkyl-linked to a triphenylphosphonium cation derivative were synthesized as H3R ligands with antioxidant properties to regulate excessive mitochondrial oxidative stress and contribute to potential new therapeutic approaches for neurodegenerative diseases. Radioligand displacement studies revealed high affinity for H3R with Ki values in the low to moderate two-digit nanomolar range for all compounds. Compound 6e showed the highest affinity (Ki H3R = 14.1 nM), comparable to that of pitolisant. Antioxidative effects were evaluated as radical-scavenging properties using the ORAC assay, in which all derivatives showed low to moderate activity. On the other hand, cytotoxic effects in SH-SY5Y neuroblastoma cells were investigated using the colorimetric alamar blue assay, which revealed significant effects on cell viability with an unequivocally structure–toxicity relationship. Finally, docking and molecular simulation studies were used to determine the H3R binding form, which will allow us to further modify the compounds to establish a robust structure-activity relationship and find a lead compound with therapeutic utility in neurodegenerative diseases.
dc.format.extent16 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/antiox13111345
dc.identifier.eissn2076-3921
dc.identifier.scopusid2-s2.0-85210438844
dc.identifier.urihttps://doi.org/10.3390/antiox13111345
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/103068
dc.identifier.wosidWOS:001363494800001
dc.information.autorucEscuela de Química; Añazco Martinez Tito Alonso; S/I; 1027543
dc.information.autorucEscuela de Química; Osses Mendoza Paula Patricia; S/I; 1135035
dc.information.autorucEscuela de Química; Salas Sánchez, Cristián Osvaldo; 0000-0001-7620-2459; 101425
dc.information.autorucEscuela de Química; Espinosa Bustos, Christian Marcelo; 0000-0001-6038-8439; 142011
dc.issue.numero11
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaAntioxidants
dc.rightsacceso abierto
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAntioxidants
dc.subjectHistamine 3 receptor
dc.subjectMolecular docking
dc.subjectMolecular dynamics
dc.subjectNeurodegenerative diseases
dc.subjectTriphenylphosphonium cation
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFirst Report on Cationic Triphenylphosphonium Compounds as Mitochondriotropic H3R Ligands with Antioxidant Properties
dc.typeartículo
dc.volumen13
sipa.codpersvinculados1027543
sipa.codpersvinculados1135035
sipa.codpersvinculados101425
sipa.codpersvinculados142011
sipa.trazabilidadORCID;2025-03-03
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