Degree: Doctor


Centro de Investigação em Química da Universidade do Porto (CIQUP)

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Showing 5 latest publications. Total publications: 27
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1. Design and synthesis of mitochondriotropic antioxidants based on dietary scaffolds endowed with neuroprotective activity and BBB permeability, Benfeito, S; Oliveira, C; Fernandes, C; Cagide, F Teixeira, J; Amorim, R; Garrido, J; Martins, C; Sarmento, B; Silva, R; Remiao, F; Uriarte, E; Oliveira, PJ; Borges, F in EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2019, ISSN: 0014-2972,  Volume: 49, 
Abstract,  Indexed in: wos  P-00Q-JHX

2. Structural elucidation of a series of benzamide derivatives, Oliveira, C; Gaspar, A Gomes, LR; Low, JN; Borges, F; Cagide, F in MAGNETIC RESONANCE IN CHEMISTRY, 2018, ISSN: 0749-1581,  Volume: 56, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1002/mrc.4682 P-00N-JWK

3. Electrochemical Behavior of a Mitochondria-Targeted Antioxidant at an Interface between Two Immiscible Electrolyte Solutions: An Alternative Approach to Study Lipophilicity, Ribeiro, JA Benfeito, S Cagide, F Teixeira, J; Oliveira, PJ; Borges, F; Silva, AF Pereira, CM in ANALYTICAL CHEMISTRY, 2018, ISSN: 0003-2700,  Volume: 90, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1021/acs.analchem.8b00787 P-00P-096
Abstract In this work, we report for the first time the accumulation activity by energized rat heart mitochondria and the ionic transfer process at a liquid liquid interface of a novel mitochondria-targeted antioxidant, named as AntiOxCIN(4), which is structurally based on a hydroxycinnamic acid. Lipophilicity studies conducted at the water/1,6-dichlorohexane (DCH) interface allowed the building up of an ionic partition diagram of AntiOxCIN(4) in accordance with the electrochemical data obtained. The partition coefficients of both positively charged (-2.3) and zwitterionic (0.2) forms of the antioxidant were determined. This study contributed to gaining an insight about the ability of the synthesized antioxidants to cross biomembrane barriers by using an interface between two immiscible electrolyte solutions (ITIES) as a model system.

4. Hydroxybenzoic Acid Derivatives as Dual-Target Ligands: Mitochondriotropic Antioxidants and Cholinesterase Inhibitors, Oliveira, C; Cagide, F Teixeira, J; Amorim, R; Sequeira, L Mesiti, F; Silva, T; Garrido, J Remiao, F; Vilar, S; Uriarte, E; Oliveira, PJ; Borges, F in FRONTIERS IN CHEMISTRY, 2018, ISSN: 2296-2646,  Volume: 6, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.3389/fchem.2018.00126 P-00N-X92
Abstract Alzheimer's disease (AD) is a multifactorial age-related disease associated with oxidative stress (OS) and impaired cholinergic transmission. Accordingly, targeting mitochondrial OS and restoring cholinergic transmission can be an effective therapeutic strategy toward AD. Herein, we report for the first time dual-target hydroxybenzoic acid (HBAc) derivatives acting as mitochondriotropic antioxidants and cholinesterase (ChE) inhibitors. The studies were performed with twomitochondriotropic antioxidants AntiOxBEN(1) (catechol derivative), and AntiOxBEN(2) (pyrogallol derivative) and compounds 15-18, which have longer spacers. Compounds AntiOxBEN(1) and 15, with a shorter carbon chain spacer (six- and eight-carbon) were shown to be potent antioxidants and BChE inhibitors (IC50 = 85 +/- 5 and 106 +/- 5 nM, respectively), while compounds 17 and 18 with a 10-carbon chain weremore effective AChE inhibitors (IC50 = 7.7 +/- 0.4 and 7.2 +/- 0.5 mu M, respectively). Interestingly, molecular modeling data pointed toward bifunctional ChEs inhibitors. The most promising ChE inhibitors acted by a non-competitive mechanism. In general, with exception of compounds 15 and 17, no cytotoxic effects were observed in differentiated human neuroblastoma (SH-SY5Y) and human hepatocarcinoma (HepG2) cells, while A beta-induced cytotoxicity was significantly prevented by the new dual-target HBAc derivatives. Overall, due to its BChE selectivity, favorable toxicological profile, neuroprotective activity and drug-like properties, which suggested blood-brain barrier (BBB) permeability, themitochondriotropic antioxidant AntiOxBEN(1) is considered a valid lead candidate for the development of dual acting drugs for AD and other mitochondrial OS-related diseases.

5. Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid, Teixeira, J; Oliveira, C; Cagide, F Amorim, R; Garrido, J Borges, F; Oliveira, PJ in JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2018, ISSN: 1475-6366,  Volume: 33, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1080/14756366.2018.1442831 P-00N-RAX
Abstract Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN(3)) based on the dietary antioxidant gallic acid was developed. AntiOxBEN(3) accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN(3) showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN(3) presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN(3) strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN(3) can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders. [GRAPHICS] .