Key Research projects

Oxidative stress-related diseases
Liver diseases
Infectious diseases
Nanomedicine
Neuroinflammation

The project embraces the discovery of NCEs acting as single or multitarget agents toward classic and non-classic therapeutics targets of neurodegenerative diseases (Alzheimer’s Disease, Parkinson’s Disease and Amyotrophic Lateral Sclerosis). The project is supported by the network of the COST Action – CA15135 Multi-target paradigm for innovative ligand identification in the drug discovery process (MuTaLig) and by national projects, namely Mito4ALS – Development of Novel Mitochondria-Targeted Antioxidants for Improving SOD1-Familial Amyotrophic Lateral Sclerosis Phenotype (POCI-01-0145-FEDER-02939; PTDC/MED-FAR/29391/2017), COMT4BRAIN-Development of Centrally-Active and Safe Catechol O-Methyltransferase Inhibitors (POCI-01-0145-FEDER-29164; PTDC/MED-QUI/29164/2017) and the Marie Sklodowska-Curie action No 895144 – Development of innovative multi-target drugs for ALS (MTD4ALS). The international and national networks ensure the mandatory computational drug design and in vivo assays.

Selected publications

Reis J, Manzella N, Cagide F, Mialet-Perez J, Uriarte E, Parini A, Borges F, Binda C. Tight-Binding Inhibition of Human Monoamine Oxidase B by Chromone Analogs: A Kinetic, Crystallographic, and Biological Analysis. J Med Chem. 2018; 61(9):4203-4212.

Silva T, Mohamed T, Shakeri A, Rao PPN, Soares-da-Silva P, Remião F, Borges F. Repurposing nitrocatechols: 5-Nitro-α-cyanocarboxamide derivatives of caffeic acid and caffeic acid phenethyl ester effectively inhibit aggregation of tau-derived hexapeptide AcPHF6. Eur J Med Chem. 2019; 167:146-152.

.Benfeito, C. Oliveira, C. Fernandes, F. Cagide, J. Teixeira, R. Amorim, J. Garrido, C. Martins, B. Sarmento, F. Remião, E. Uriarte, P. J. Oliveira, F. Borges “Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction” Eur. J. Med. , 2019, 167, 525-545.

Liver diseases

The project is focused on the discovery of new chemical entities for Non-Alcoholic Fatty Liver Disease (NAFLD), including its main pathologic outcome the non-alcoholic steatohepatitis (NASH). The research is sustained by two European projects (FOIE GRAS, H2020MSCA-ITN- Bioenergetic Remodeling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease and mtFOIE GRAS, MSCA-RISE- Non-invasive Profiling of Mitochondrial Function in Non-Alcoholic Fatty Liver Disease) and a national project PTDC/DTP-FTO/2433/2014 – MitoBOOST: A Next-Generation Therapeutics for Non-Alcoholic Fatty Liver Disease Based on Smart Antioxidant Delivery to Mitochondria. The international and national networks ensure the mandatory biological screenings and in vivo assays needed for the rational drug discovery project.

Selected publications

Teixeira J, Oliveira C, Cagide F, Amorim R, Garrido J, Borges F, Oliveira PJ. Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid. J Enzyme Inhib Med Chem. 2018; 33(1):567-576.

Teixeira J, Oliveira C, Amorim R, Cagide F, Garrido J, Ribeiro J, Pereira CM, Silva AF, Andrade PB, Oliveira PJ, Borges F. Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria. Sci Rep. 2017; 7(1):6842.

Teixeira J, Cagide F, Benfeito S, Soares P, Garrido J, Baldeiras I, Ribeiro JA, Pereira CM, Silva AF, Andrade PB, Oliveira PJ, Borges F. Development of a Mitochondriotropic Antioxidant Based on Caffeic Acid: Proof of Concept on Cellular and Mitochondrial Oxidative Stress Models. J Med Chem. 2017; 60(16):7084-7098.

Infectious diseases

Infectious diseases

One of the key aims of the project is the discovery of new antibacterial, antifungal and/or antibiofilm agents (following single target or multitarget strategies) to fuel the antimicrobial armamentarium. The project is focused on innovative drug discovery strategies based on privileged scaffolds and drug repurposing, which are ahead from the me-too and me-better approaches used so far by pharma industry. To speed up the process, the group established several collaborations, including with CO-ADD (Community for Open Antimicrobial Drug Discovery) and the LEPABE research center. The project is also supported by the network of CA15135 Multi-target paradigm for innovative ligand identification in the drug discovery process (MuTaLig) and the national projects ABFish – Development of new antibiotics for aquaculture (POCI-01-0145-FEDER-028397; PTDC/ASP-PES/28397/2017) and BOFILM – Development of novel biocide solutions for effective biofilm control (POCI-01-0145-FEDER-030219/2017; PTDC/BII-BTI/30219/2017).

Selected publications

Oliveira IM, Borges A, Borges F, Simões M. Repurposing ibuprofen to control Staphylococcus aureus biofilms. Eur J Med Chem. 2019; 166:197-205.

Borges A, Sousa P, Gaspar A, Vilar S, Borges F, Simões M. Furvina inhibits the 3-oxo-C12-HSL-based quorum sensing system of Pseudomonas aeruginosa and QS-dependent phenotypes. Biofouling. 2017; 33(2):156-168.

Borges A, Abreu AC, Dias C, Saavedra MJ, Borges F, Simões M. New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms. Molecules. 2016; 21(7).

Nanomedicine

The group is engaged in the development of innovative therapeutic solutions using different nanocarriers and nanoformulations. This strategy provides an outstanding platform to improve pharmacokinetics and modulate ADMET properties, mainly water solubility, membrane permeability and metabolic stability. The project is sustained by strong collaborations with national and international organisations and by the European Technology Platform on Nanomedicine.

Selected publications

Fernandes C, Martins C, Fonseca A, Nunes R, Matos M J, Silva R, Garrido J, Sarmento B, Remião F, Espinar-Otero F, Uriarte E, Borges F. PEGylated PLGA Nanoparticles as a Smart Carrier to Increase the Cellular Uptake of a Coumarin-Based Monoamine Oxidase B Inhibitor, ACS Appl. Mater., 2018, 10:39557–39569.

Fernandes C, Benfeito S, Amorim R, Teixeira J, Oliveira P J, Remião F, Borges F. Desrisking the Cytotoxicity of a Mitochondriotropic Antioxidant Based on Caffeic Acid by a PEGylated Strategy, Bioconjug. Chem., 2018, 29:2723–2733.

Fernandes C, Pinto M, Martins C, Gomes M J, Sarmento B, Oliveira P J, Remião F, Borges F. Development of a PEGylated-based Platform for Efficient Delivery of Dietary Antioxidants Across the Blood–Brain Barrier, Bioconjug. Chem., 2018, 29:1677-1689.

nanomedicine

Neuroinflammation

Among potential regulators of neuroinflammation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) emerged as a promising drug target. The group is devoted to the discovery of reliable, selective bona fide NOX2 inhibitors with application in basic and applied research. The inhibitors developed in this project can be used not only to clearly elucidate the pathophysiological roles of NOX2, but also for its validation as a therapeutic target for neurodegenerative diseases. The project is conducted in close collaboration with Prof. Dr. Mattevi’s Group (Biocry laboratory www.unipv.it/biocry) at the Department of Biology and Biotechnology of the University of Pavia (UNIPV, Italy).

Selected publications

J. Reis, M. Massari, S. Marchese, M. Ceccon, F.S. Aalbers, F. Corana, S. Valente, A. Mai, F. Magnani, A. Mattevi, A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action, Redox Biol. 2020, 32: 101466.