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Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor

2022Journal article Restricted access
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dc.contributor.authorChavarria, Daniel
dc.contributor.authorBenfeito, Sofia
dc.contributor.authorSoares, Pedro
dc.contributor.authorLima, Carla
dc.contributor.authorGarrido, Jorge
dc.contributor.authorSerrão, Paula
dc.contributor.authorSoares-da-Silva, Patrício
dc.contributor.authorRemião, Fernando
dc.contributor.authorOliveira, Paulo J.
dc.contributor.authorBorges, Fernanda
dc.date.accessioned2023-02-14T16:28:38Z
dc.date.embargo2035-12-31
dc.date.issued2022
dc.description.abstractIncreased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD.pt_PT
dc.description.sponsorshipThis work was funded by FEDER sfunds through the Operational Programme Competitiveness Factors-COMPETE and national funds by FCT – Foundation for Science and Technology under research grants (Grants UIDB/00081/2020 (CIQUP), PTDC/MED-QUI/29164/2017 – POCI-01-0145-FEDER-29164, LA/P/0056/2020 (IMS), UIDB/04539/ 2020, UIDP/04539/2020, OPENSCREEN-NORTE-01-0145-FEDER- 085468. DC thanks FCT, POPH, FEDER/COMPETE for his grant. SB and PS grants are supported by PT-OPENSCREEN-NORTE-01-0145- FEDER-085468 project.
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejmech.2022.114740pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/22276
dc.language.isoengpt_PT
dc.publisherElsevierpt_PT
dc.relationPOCI-01-0145-FEDER-29164
dc.relationChemistry Research Unit of University of Porto
dc.relationUIDB/04539/ 2020
dc.relationOPENSCREEN-NORTE-01-0145-FEDER- 085468
dc.relationOPENSCREEN-NORTE-01-0145- FEDER-085468
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0223523422006420?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectParkinson’s diseasept_PT
dc.subjectCaffeic acidpt_PT
dc.subjectAntioxidantspt_PT
dc.subjectCatechol-O-Methyltransferasept_PT
dc.subjectMonoamine oxidasept_PT
dc.subjectNeuroprotectionpt_PT
dc.titleBoosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitorpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleChemistry Research Unit of University of Porto
oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00081%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FMED-QUI%2F29164%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04539%2F2020/PT
oaire.citation.startPage114740pt_PT
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume243pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream9471 - RIDTI
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGarrido
person.givenNameJorge
person.identifier.orcid0000-0001-8981-231X
person.identifier.scopus-author-id7202779733
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoveryf548e711-c68e-4c49-9471-9923c047116d
relation.isProjectOfPublication2a43ea7f-a750-492c-bafc-d818da22f041
relation.isProjectOfPublication54872a2a-e0fe-49b0-8c18-249c9dfb7fe6
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