Bisavenathramide Analogues as Nrf2 Inductors and Neuroprotectors in In Vitro Models of Oxidative Stress and Hyperphosphorylation

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dc.contributor.authorCores Esperón, Ángel
dc.contributor.authorAbril Comesaña, Sheila
dc.contributor.authorMichalska Dziama, Patrycja
dc.contributor.authorDuarte, Pablo
dc.contributor.authorOlives Barba, Ana Isabel
dc.contributor.authorMartín Carmona, María Antonia
dc.contributor.authorVillacampa Sanz, Mercedes
dc.contributor.authorLeón Martínez, Rafael
dc.contributor.authorMenéndez Ramos, José Carlos
dc.date.accessioned2023-06-17T08:25:53Z
dc.date.available2023-06-17T08:25:53Z
dc.date.issued2021-06-10
dc.description.abstractOxidative stress is crucial to the outbreak and advancement of neurodegenerative diseases and is a common factor to many of them. We describe the synthesis of a library of derivatives of the 4-arylmethylen-2-pyrrolin-5-one framework by sequential application of a three-component reaction of primary amines, β-dicarbonyl compounds, and α-haloketones and a Knoevenagel condensation. These compounds can be viewed as cyclic amides of caffeic and ferulic acids, and are also structurally related to the bisavenanthramide family of natural antioxidants. Most members of the library showed low cytotoxicity and good activity as inductors of Nrf2, a transcription factor that acts as the master regulator of the antioxidant response associated with activation of the antioxidant response element (ARE). Nrf2-dependent protein expression was also proved by the significant increase in the levels of the HMOX1 and NQO1 proteins. Some compounds exerted neuroprotective properties in oxidative stress situations, such as rotenone/oligomycin-induced toxicity, and also against protein hyperphosphorylation induced by the phosphatase inhibitor okadaic acid. Compound 3i, which can be considered a good candidate for further hit-to-lead development against neurodegenerative diseases due to its well-balanced multitarget profile, was further characterized by proving its ability to reduce phosphorylated Tau levels.
dc.description.departmentDepto. de Química en Ciencias Farmacéuticas
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipFederación Española de Enfermedades Raras
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/71862
dc.identifier.citationCores, Ángel, et al. «Bisavenathramide Analogues as Nrf2 Inductors and Neuroprotectors in In Vitro Models of Oxidative Stress and Hyperphosphorylation». Antioxidants, vol. 10, n.o 6, junio de 2021, p. 941. DOI.org (Crossref), https://doi.org/10.3390/antiox10060941.
dc.identifier.doi10.3390/antiox10060941
dc.identifier.issn2076-3921
dc.identifier.officialurlhttps://doi.org/10.3390/antiox10060941
dc.identifier.relatedurlhttps://www.mdpi.com/journal/antioxidants
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7089
dc.issue.number6
dc.journal.titleAntioxidants
dc.language.isoeng
dc.page.initial941
dc.publisherMDPI
dc.relation.projectIDinfo:eu-repo/grantAgreement/RTI2018-097662-B-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI17/01700
dc.relation.projectID info:eu-repo/grantAgreement/B2017/BMD-3813
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI20/00433
dc.relation.projectIDinfo:eu-repo/grantAgreement/B2017/BMD-3827
dc.rightsATTRIBUTION 4.0 INTERNATIONAL
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.cdu547
dc.subject.keywordNrf2–ARE pathway
dc.subject.keywordNeurodegenerative diseases
dc.subject.keywordOxidative stress
dc.subject.keywordKeap1
dc.subject.keywordNrf2 regulation
dc.subject.keywordBisavenanthramides
dc.subject.ucmQuímica orgánica (Farmacia)
dc.titleBisavenathramide Analogues as Nrf2 Inductors and Neuroprotectors in In Vitro Models of Oxidative Stress and Hyperphosphorylation
dc.typejournal article
dc.volume.number10
dspace.entity.typePublication
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