Degree: Doctor

Affiliation(s):

CIQUP-IMS, ISEP, Polytechnic of Porto, 4249-015 Porto, Portugal

Bio

Jorge Garrido, professor at the Instituto Superior de Engenharia do Porto, Department for Engineering Chemistry, holds a PhD in Biochemistry. Jorge teaches undergraduate courses such as Analytical and Organic Chemistry labs, Instrumental Methods of Analysis labs, Natural Products and Quality Bioproducts and the course of Laboratory of Energy I at Chemical Engineering Master degree. He was Deputy Director of Chemical Engineering Degree between 2010 and 2018 and since 2015 Director of Bioresources Degree. He has been a researcher of international and national projects in the area of interface of Analytical Chemistry and (Bio)Organic Chemistry, some of them in collaboration with the Portuguese Industry. Present research interests include Sustainable Advanced Materials, Bioelectrochemistry, Nanotechnology and Nanomedicine. He has experience as scientific supervisor of Post-doc, PhD, Master projects and industrial Internships. He is author of 6 book chapters and 101 publications in SCI journals (h-index = 36).

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Publications
Showing 5 latest publications. Total publications: 58
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1. PEGylated PLGA Nanoparticles As a Smart Carrier to Increase the Cellular Uptake of a Coumarin-Based Monoamine Oxidase B Inhibitor, Fernandes, C; Martins, C; Fonseca, A; Nunes, R; Matos, MJ; Silva, R; Garrido, J Sarmento, B; Remiao, F; Otero Espinar, FJ; Uriarte, E; Borges, F in ACS APPLIED MATERIALS & INTERFACES, 2018, ISSN: 1944-8244,  Volume: 10, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1021/acsami.8b17224 P-00P-WD2
Abstract Despite research efforts to discover new drugs for Parkinson treatment, the majority of candidates fail in preclinical and clinical trials due to inadequate pharmacokinetic properties, namely blood-brain barrier permeability. Within the high demand to introduce new drugs to market, nano technology can be used as a solution. Accordingly, PEGylated PLGA nano particles (NPs) were used as a smart delivery carrier to solve the suboptimal aqueous solubility, which precludes its use in in vivo assays, of a potent, reversible, and selective monoamine oxidase B inhibitor (IMAO-B) (coumarin C75, IC50 = 28.89 +/- 1.18 nM). Long-term stable PLGA@C75 NPs were obtained by nanoprecipitation method, with sizes around 105 nm and a zeta potential of -10.1 mV. The encapsulation efficacy was around 50%, achieving the final C75 concentration of 807 +/- 30 mu M in the nano formulation, which corresponds to a therapeutic concentration 27828-fold higher than its IC50 value. Coumarin C75 showed cytotoxic effects at 50 mu M after 48 and 72 h of exposure in SH-SY5Y, Caco-2, and hCMEC/D3 cell lines. Remarkably, no cytotoxic effects were observed after nanoencapsulation. Furthermore, the data obtained from the P-gp-Glo assay and the cellular uptake studies showed that C75 is a P-glycoprotein (P-gp) substrate having a lower uptake profile in intestinal and brain endothelial cells. Moreover, it was shown that this membrane transporter influences C75 permeability profile in Caco-2 and hCMEC/D3 cells. Interestingly, PLGA NPs inhibited P-gp and were able to cross intestinal and brain membranes allowing the successful transport of C75 through this type of biological barriers. Overall, this work showed that nanotechnology can be used to solve drug discovery related drawbacks.

2. 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.

3. Disruption of mitochondrial function as mechanism for anti-cancer activity of a novel mitochondriotropic menadione derivative, Teixeira, J; Amorim, R; Santos, K; Soares, P; Datta, S; Cortopassi, GA; Serafim, TL; Sardao, VA; Garrido, J Borges, F; Oliveira, PJ in TOXICOLOGY, 2018, ISSN: 0300-483X,  Volume: 393, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1016/j.tox.2017.11.014 P-00N-8Q9
Abstract Menadione, also known as vitamin K-3, is a 2-methyl-1,4 naphthoquinone with a potent cytotoxic activity mainly resulting from its quinone redox-cycling with production of reactive oxygen species (ROS). Although increased ROS generation is considered a relevant mechanism in cancer cell death, it may not be sufficiently effective to kill cancer cells due to phenotypic adaptations. Therefore, combining ROS-generating agents with other molecules targeting important cancer cell phenotypes can be an effective therapeutic strategy. As mitochondrial dysfunction has been implicated in many human diseases, including cancer, we describe here the discovery of a mitochondrial-directed agent (MitoK(3)), which was developed by conjugating a TPP cation to the C3 position of the menadione's naphthoquinone ring, increasing its selective accumulation in mitochondria, as well as led to alterations of its redox properties and consequent biological outcome. MitoK(3) disturbed the mitochondrial bioenergetic apparatus, with subsequent loss of mitochondrial ATP production. The combinatory strategy of MitoK3 with anticancer agent doxorubicin (DOX) resulted in a degree of cytotoxicity higher than those of the individual molecules, as the combination triggered tumour apoptotic cell death evident by caspase 3/9 activities, probably through mitochondrial destabilization or by interference with mitochondrial redox processes. The results of this investigation support the importance of drug discovery process in developing molecules that can be use as adjuvant therapy in patients with specific cancer subtypes.

4. 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] .

5. Exploring nature profits: Development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids, Teixeira, J; Silva, T; Benfeito, S Gaspar, A Manuela Garrido, EM Garrido, J Borges, F in EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, ISSN: 0223-5234,  Volume: 62, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1016/j.ejmech.2012.12.049 P-005-1RV
Abstract Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloyl cinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structure property activity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloyl cinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.