Degree: Doctor

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FCUP

Bio

Fernanda Borges (FB) is an Associate Professor with habilitation at the Department of Chemistry and Biochemistry. She received her MSc and PhD (Pharmaceutical Chemistry) in Pharmacy from the Faculty of Pharmacy, University of Porto, Portugal. FB is the coordinator of the Medicinal and Biological Chemistry Group (https://drugdiscoveryup.pt/), of the Chemistry Research Centre of the University of Porto (CIQUP).  The Group is internationally competitive and rmultidisciplinary working at the chemistry–biology interface R&D areas related to human health and well-being. The team is composed of researchers with diverse backgrounds, from chemistry and biochemistry to pharmacy and nanotechnology, and has expertise in drug discovery, drug analysis, and drug delivery FB published 407 articles, 26 book chapters (H-index: 57; Scopus) and received 9 awards. Supervised/co-supervised (inter)national students at PhD (36) and MSc (35) thesis and 14 postDocs and researcher fellows/grant holders. FB is the principal Investigator (PI) and Co-PI of 33 national and european projects, and principal inventor in 8 (inter)national patents. Her research is focused in the design and development of new chemical entities for the prevention/therapy of neurodegenerative, liver, cancer or infectious diseases.




Publications
Showing 5 latest publications. Total publications: 322
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1. Aloe vera―An Extensive Review Focused on Recent Studies, Catalano, A; Ceramella, J; Iacopetta, D; Marra, M; Conforti, F; Lupi, FR; Gabriele, D; Borges, F Sinicropi, MS in FOODS, 2024, ISSN: 2304-8158,  Volume: 13, 
Review,  Indexed in: crossref, scopus, unpaywall, wos  DOI: 10.3390/foods13132155 P-010-YXZ
Abstract Since ancient times, Aloe vera L. (AV) has attracted scientific interest because of its multiple cosmetic and medicinal properties, attributable to compounds present in leaves and other parts of the plant. The collected literature data show that AV and its products have a beneficial influence on human health, both by topical and oral use, as juice or an extract. Several scientific studies demonstrated the numerous biological activities of AV, including, for instance, antiviral, antimicrobial, antitumor, and antifungal. Moreover, its important antidepressant activity in relation to several diseases, including skin disorders (psoriasis, acne, and so on) and prediabetes, is a growing field of research. This comprehensive review intends to present the most significant and recent studies regarding the plethora of AV's biological activities and an in-depth analysis exploring the component/s responsible for them. Moreover, its morphology and chemical composition are described, along with some studies regarding the single components of AV available in commerce. Finally, valorization studies and a discussion about the metabolism and toxicological aspects of this Wonder Plant are reported.

2. Discovery of a Potent, Selective, and Blood-Brain Barrier Permeable Non-nitrocatechol Inhibitor of Catechol-<i>O</i>-methyltransferase, Benfeito, S; Albuquerque, B; Sequeira, L; Lima, C; Chavarria, D; Serrao, P; Cagide, F; Soares da Silva, P; Borges, F in JOURNAL OF MEDICINAL CHEMISTRY, 2024, ISSN: 0022-2623,  Volume: 67, 
Article,  Indexed in: crossref, scopus, unpaywall, wos  DOI: 10.1021/acs.jmedchem.4c01682 P-017-3YE
Abstract A new library of non-nitrocatechol compounds (HetCAMs) was developed and their efficacy was compared to tolcapone, a standard COMT inhibitor for PD. Compound 9 emerged as the most potent inhibitor, showing selective inhibition of brain (IC50 = 24 nM) and liver (IC50 = 81 nM) MB-COMT over liver S-COMT (IC50 = 620 nM) isoforms. Although compound 9 presented higher IC50 values than tolcapone, it was more selective for brain MB-COMT than liver S-COMT. Unlike tolcapone, compound 9 is not a tight-binding inhibitor and is less cytotoxic to HepG2 and SK-N-SH cells. Additionally, compound 9 is predicted to cross the blood-brain barrier (BBB) by passive diffusion and chelate divalent metals like Fe(II) and Cu(II). The results demonstrate the potential of this rational drug design strategy for developing new CNS-active drug candidates, offering symptom relief via COMT inhibition that can provide a long-term, disease-modifying outcome (chelation of divalent metals) in PD.

3. Mitochondria dysfunction induced by decyl-TPP mitochondriotropic antioxidant based on caffeic acid AntiOxCIN6 sensitizes cisplatin lung anticancer therapy due to a remodeling of energy metabolism, Amorim, R; Magalhaes, CC; Benfeito, S; Cagide, F; Tavares, LC; Santos, K; Sardao, VA; Datta, S; Cortopassi, GA; Baldeiras, I; Jones, JG; Borges, F Oliveira, PJ; Teixeira, J in BIOCHEMICAL PHARMACOLOGY, 2024, ISSN: 0006-2952,  Volume: 219, 
Article,  Indexed in: crossref, scopus, wos  DOI: 10.1016/j.bcp.2023.115953 P-00Z-ESJ
Abstract The pharmacological interest in mitochondria is very relevant since these crucial organelles are involved in the pathogenesis of multiple diseases, such as cancer. In order to modulate cellular redox/oxidative balance and enhance mitochondrial function, numerous polyphenolic derivatives targeting mitochondria have been developed. Still, due to the drug resistance emergence in several cancer therapies, significant efforts are being made to develop drugs that combine the induction of mitochondrial metabolic reprogramming with the ability to generate reactive oxygen species, taking into consideration the varying metabolic profiles of different cell types. We previously developed a mitochondria-targeted antioxidant (AntiOxCIN6) by linking caffeic acid to lipophilic triphenylphosphonium cation through a 10-carbon aliphatic chain. The antioxidant activity of AntiOxCIN6 has been documented but how the mitochondriotropic compound impact energy metabolism of both normal and cancer cells remains unknown. We demonstrated that AntiOxCIN6 increased antioxidant defense system in HepG2 cells, although ROS clearance was ineffective. Consequently, AntiOxCIN6 significantly decreased mitochondrial function and morphology, culminating in a decreased capacity in complex I-driven ATP production without affecting cell viability. These alterations were accompanied by an increase in glycolytic fluxes. Additionally, we demonstrate that AntiOxCIN6 sensitized A549 adenocarcinoma cells for CIS-induced apoptotic cell death, while AntiOxCIN6 appears to cause metabolic changes or a redox pre-conditioning on lung MRC-5 fibroblasts, conferring protection against cisplatin. We propose that length and hydrophobicity of the C10-TPP+ alkyl linker play a significant role in inducing mitochondrial and cellular toxicity, while the presence of the antioxidant caffeic acid appears to be responsible for activating cytoprotective pathways.

4. Biological and Medicinal Properties of Natural Chromones and Chromanones, Gaspar, A Garrido, EMPJ; Borges, F Garrido, JMPJ in ACS OMEGA, 2024, ISSN: 2470-1343, 
Review,  Indexed in: crossref, scopus, unpaywall, wos  DOI: 10.1021/acsomega.4c00771 P-010-F4M
Abstract Emerging threats to human health require a concerted effort to search for new treatment therapies. One of the biggest challenges is finding medicines with few or no side effects. Natural products have historically contributed to major advances in the field of pharmacotherapy, as they offer special characteristics compared to conventional synthetic molecules. Interest in natural products is being revitalized, in a continuous search for lead structures that can be used as models for the development of new medicines by the pharmaceutical industry. Chromone and chromanones are recognized as privileged structures and useful templates for the design of diversified therapeutic molecules with potential pharmacological interest. Chromones and chromanones are widely distributed in plants and fungi, and significant biological activities, namely antioxidant, anti-inflammatory, antimicrobial, antiviral, etc., have been reported for these compounds, suggesting their potential as lead drug candidates. This review aims to update the literature published over the last 6 years (2018-2023) regarding the natural occurrence and biological activity of chromones and chromanones, highlighting the recent findings and the perspectives that they hold for future research and applications namely in health, cosmetic, and food industries.

5. Dual Inhibitors of Brain Carbonic Anhydrases and Monoamine Oxidase-B Efficiently Protect against Amyloid-β-Induced Neuronal Toxicity, Oxidative Stress, and Mitochondrial Dysfunction, Carradori, S; Chavarria, D Provensi, G; Leri, M; Bucciantini, M; Carradori, S; Bonardi, A; Gratteri, P; Borges, F Nocentini, A; Supuran, CT in JOURNAL OF MEDICINAL CHEMISTRY, 2024, ISSN: 0022-2623,  Volume: 67, 
Article,  Indexed in: crossref, scopus, unpaywall, wos  DOI: 10.1021/acs.jmedchem.4c00045 P-010-2GH
Abstract We report here the first dual inhibitors of brain carbonic anhydrases (CAs) and monoamine oxidase-B (MAO-B) for the management of Alzheimer's disease. Classical CA inhibitors (CAIs) such as methazolamide prevent amyloid-beta-peptide (A beta)-induced overproduction of reactive oxygen species (ROS) and mitochondrial dysfunction. MAO-B is also implicated in ROS production, cholinergic system disruption, and amyloid plaque formation. In this work, we combined a reversible MAO-B inhibitor of the coumarin and chromone type with benzenesulfonamide fragments as highly effective CAIs. A hit-to-lead optimization led to a significant set of derivatives showing potent low nanomolar inhibition of the target brain CAs (K(I)s in the range of 0.1-90.0 nM) and MAO-B (IC50 in the range of 6.7-32.6 nM). Computational studies were conducted to elucidate the structure-activity relationship and predict ADMET properties. The most effective multitarget compounds totally prevented A beta-related toxicity, reverted ROS formation, and restored the mitochondrial functionality in an SH-SY5Y cell model surpassing the efficacy of single-target drugs.