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

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Chavarria, D (Author) Other; Benfeito, S (Author) Other; Soares, P (Author) FCUP; Lima, C (Author) Other; Garrido, J (Author) Other; Maria Paula Serrão (Author) FMUP; Soares da Silva, P (Author) Other; Fernando Remiao (Author) FFUP; Oliveira, PJ (Author) Other; Fernanda Borges (Author) FCUP

Journal

Title: European Journal of Medicinal Chemistry

Vol. 243

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00X-6YY

DOI: 10.1016/j.ejmech.2022.114740

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15