Portal de investigação
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor
Autores da FMUP
Participantes de fora da FMUP
- Chavarria, D
- Benfeito, S
- Soares, P.
- Lima, C
- Garrido, J
- Remia, F
- Oliveira, PJ
- Borges, M.
Unidades de investigação
Abstract
Increased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neuro-degeneration 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. alpha-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low mu M IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low mu M range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 mu M. 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 mu M protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffu-sion. 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.
Copyright © 2022 Elsevier Masson SAS. All rights reserved.
Dados da publicação
- ISSN/ISSNe:
- 1768-3254, 1768-3254
- Tipo:
- Article
- Páginas:
- 114740-114740
- Link para outro recurso:
- www.scopus.com
European Journal of Medicinal Chemistry Elsevier Masson s.r.l.
Citações Recebidas na Web of Science: 8
Citações Recebidas na Scopus: 10
Documentos
- Não há documentos
Filiações
Keywords
- Parkinson?s disease; Caffeic acid; Antioxidants; Catechol-O-Methyltransferase; Monoamine oxidase; Neuroprotection
Financiamento
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Citar a publicação
Chavarria D,Benfeito S,Soares P,Lima C,Garrido J,Serra P,Soares da Silva P,Remia F,Oliveira PJ,Borges M. Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor. Eur. J. Med. Chem. 2022. 243. p. 114740-114740. IF:6,700. (1).
