Showing: 10 from total: 2087 publications
11. Nanoporous anodic alumina layers obtained from novel deep eutectic solvent formulations
Fernandes, PMV ; Brincoveanu, O ; Pantazi, A ; Petica, A ; Pereira, CM ; Silva, AF ; Enachescu, M ; Anicai, L
Article,  Indexed in: crossref, scopus, unpaywall, wos 
Abstract The possible fabrication of porous anodic oxide films on aluminium in ionic liquids based on choline dihydrogen citrate eutectic mixtures both with oxalic acid and isopropyl alcohol and ethylene glycol, has been investigated. The anodisation has been carried out in either potentiostatic or galvanostatic regime, at temperatures of 45-80 degrees C, for different process durations. Quite compact, uniform anodic alumina layers have been obtained. Based on AFM and SEM investigations, pore diameters between 50 and 80 nm and interpore distances in the range of 160-200 nm have been estimated, with values influenced by the electrolyte type and anodisation conditions. The highest anodisation rate of about 0.4 mu m min(-1) has been determined by applying operation temperatures of 60 degrees C. The recorded EIS spectra showed a pure capacitive behaviour and high anodic oxide resistances of 10(6)-10(7) omega cm(2) order.

12. Drivers of FDI in small states
Forte, R ; Neves, C
in JOURNAL OF THE ASIA PACIFIC ECONOMY, 2023, ISSN: 1354-7860,  Volume: 28, 
Article,  Indexed in: crossref, scopus, wos 
Abstract This paper examines the determinants of FDI in small states, as only a small number of studies have analyzed the determinants of FDI in these countries. Small states have particular features that justify the need for a deeper analysis. Based on a panel data for 42 small states between 2005 and 2019, results clearly indicate the importance of the quality of human capital and the availability of infrastructures as the strongest drivers of FDI in small states. The country's level of openness, the availability of natural resources, the level of corporate tax and control of corruption also seems to play a relevant role therein. Moreover, the results suggest that the determinants differ depending on the region to which the country belongs and differ between island and non-island countries. These results can help small countries in defining policies that help them to attract FDI, which is crucial for their sustainable development.

13. Assessment of Surface Water Quality Using the Water Quality Index (IWQ), Multivariate Statistical Analysis (MSA) and Geographic Information System (GIS) in Oued Laou Mediterranean Watershed, Morocco
Azhari, HE ; Cherif, EK ; Sarti, O ; Azzirgue, EM ; Dakak, H ; Yachou, H ; Esteves da Silva, JCG ; Salmoun, F
in Water (Switzerland), 2023, ISSN: 2073-4441,  Volume: 15, 
Article,  Indexed in: crossref, scopus 
Abstract Surface water is used for a variety of purposes, including agriculture, drinking water, and other services. Therefore, its quality is crucial for irrigation, human welfare, and health. Thus, the main objective is to improve surface water quality assessment and geochemical analysis to evaluate anthropogenic activities’ impact on surface water quality in the Oued Laou watershed, Northern Morocco. Thirteen surface water samples were characterized for 26 physicochemical and biological parameters. In this aspect, emerging techniques such as multivariate statistical approaches (MSA), water quality indices (WQI), irrigation water quality (IWQI), and Geographic Information System (GIS) were employed to identify the sources of surface water pollution, their suitability for consumption, and the distribution of surface water quality. The results showed that the major ion concentrations were reported in the following order: Ca2+, Na+, Mg2+, and K+; and HCO3− > CO32− > Cl− > SO42− > NO3− > F− > PO43− > NO2−. It was also demonstrated that almost all parameters had concentrations lower than World Health Organization (WHO) limits, except for bicarbonate ions (HCO3−) and the biochemical oxygen demand for five days (BOD5), which exceeded the WHO limits at 120 mg/L and 3 mg/L, respectively. Furthermore, the types of Ca2+-HCO3− (Calcium-Bicarbonate) and Ca2+-Mg2+-HCO3− (Calcium-Magnesium-Bicarbonate) predominated in surface water. The Principal Component Analysis (PCA) indicates that the Oued Laou river was exposed to two forms of contamination, the first being attributed to anthropogenic activities such as agriculture, while the second reflects the water-sediment interaction. The Hierarchical Cluster Analysis (HCA), reflecting the mineralization in the study area, has classified the samples into four clusters. The Inverse Distance Weighting (IDW) of the WQI indicates that 7.69% and 38.46% of the surface water represent, respectively, excellent and good quality for drinking. At the same time, the IWQI revealed that 92.30% of the water surface is good for irrigation. As a result, the combination of WQIs, PCA, IWQI, and GIS techniques is effective in providing clear information for assessing the suitability of surface water for drinking and its controlling factors and can also support decision-making in susceptible locations such as the Oued Laou river in northern Morocco. © 2022 by the authors.

14. Phytochemical Compounds and Anticancer Activity of Cladanthus mixtus Extracts from Northern Morocco
El Mihyaoui, A ; Charfi, S ; Erbiai, EH ; Pereira, M ; Duarte, D ; Vale, N ; Candela Castillo, ME ; Badoc, A ; Lamarti, A ; Esteves da Silva, JCG ; Arnao, MB
in Cancers, 2023, ISSN: 2072-6694,  Volume: 15, 
Article,  Indexed in: crossref, scopus 
Abstract Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts of roots, stems, leaves, and flowers from Cladanthus mixtus. The anticancer activity was evaluated in vitro against two cancer cell lines: human breast carcinoma (MCF-7) and human prostate carcinoma (PC-3), using the MTT assay and microscopic observation. A human normal lung fibroblast (MRC-5) was included to determine the extract’s safety for non-tumoral cells. The chemical composition results by LC-MS analysis revealed the presence of 24 phenolic compounds. Furthermore, GC-MS analysis allowed the identification of many biomolecules belonging to terpenoids, esters, alcohols, alkanes, fatty acids, organic acids, benzenes, phenols, ketones, carbonyls, amines, sterols, and other groups. The findings suggest that the majority of C. mixtus extracts have antiproliferative activity against two cancer cell lines, MCF-7 and PC-3, and one non-tumoral cell line, MRC-5. The activity was dose-dependent, and the highest effect was obtained with leaf extract in the two cancer cell lines. Moreover, these extracts demonstrated an acceptable toxicological profile against normal cells. Overall, C. mixtus extracts revealed promising antitumor properties provided by their phytochemical composition. © 2022 by the authors.

15. Early Activation of Antioxidant Responses in Ni-Stressed Tomato Cultivars Determines Their Resilience Under Co-exposure to Drought
Spormann, S ; Soares, C ; Martins, V ; Azenha, M ; Gerós, H ; Fidalgo, F
in JOURNAL OF PLANT GROWTH REGULATION, 2023, ISSN: 0721-7595,  Volume: 42, 
Article,  Indexed in: crossref, scopus, wos 
Abstract Throughout their life cycle, plants are subjected to a variety of environmental constraints, including abiotic stresses. The present study aimed at characterizing the responses of the two tomato cultivars Gold Nugget (GN) and Purple Calabash (PC) exposed to a combination of nickel (Ni) and drought. The following hypotheses were pursued: (i) the activation of responses to one stressor eases further adjustments to a second stressor; and (ii) the two tomato cultivars are differentially susceptible to drought and heavy metal-stress. Besides biometrical evaluations, the distribution of Ni in tissues and the redox homeostasis in both cultivars were compared in response to Ni-stress, polyethylene glycol (PEG)-induced drought, and to their combination. Regarding single stresses, Ni caused more harmful effects to plants than PEG-induced drought, in terms of growth inhibition and production of reactive oxygen species. Ni was mostly accumulated in the roots. The GN cultivar promptly activated antioxidant defenses under Ni-stress, while, in PC, such antioxidants were more strongly induced under combined stress. Stress co-exposure led to a drastic proline accumulation, resembling a signal of stress sensitivity. Overall, the GN cultivar seemed to be less susceptible to the combined stress than PC, as it could activate stronger antioxidant defenses under single Ni toxicity, possibly easing further adjustments demanded by the later co-exposure to drought. This study showed that the two cultivars of the same species had different levels of perception and responsiveness to Ni-induced stress, which translated into different susceptibilities to the combined exposure to PEG-induced drought. [GRAPHICS] .

16. Propargylamine: an important moiety in drug discovery
Carneiro, A ; Uriarte, E ; Borges, F ; Matos, MJ
in FUTURE MEDICINAL CHEMISTRY, 2023, ISSN: 1756-8919,  Volume: 15, 
Review,  Indexed in: crossref, scopus, wos 
Abstract Propargylamine is a chemical moiety whose properties have made it a widely distributed group within the fields of medicinal chemistry and chemical biology. Its particular reactivity has traditionally popularized the preparation of propargylamine derivatives using a large variety of synthetic strategies, which have facilitated the access to these compounds for the study of their biomedical potential. This review comprehensively covers and analyzes the applications that propargylamine-based derivatives have achieved in the drug discovery field, both from a medicinal chemistry perspective and from a chemical biology-oriented approach. The principal therapeutic fields where propargylamine-based compounds have made an impact are identified, and a discussion of their influence and growing potential is included. Tweetable abstractPropargylamine derivatives are commonly present in various areas of #drugdiscovery. In this new @fsgfmc review article, scientists @aitorcarneiro and @mariacmatos from @UPorto and @UniversidadeUSC discuss the reasons underlying recent uses and applications of these compounds.

17. Sulfonamide a Valid Scaffold for Antioxidant Drug Development
Egbujor, MC ; Garrido, J ; Borges, F ; Saso, L
in MINI-REVIEWS IN ORGANIC CHEMISTRY, 2023, ISSN: 1570-193X,  Volume: 20, 
Review,  Indexed in: crossref, wos 
Abstract Like the well-known sulfa drugs, Sulfonamides are ascribed to a myriad of biological activities, including antioxidant activity. In fact, several tertiary sulfonamides, particularly N, N-disubstituted analogues, are recognized as antioxidants that can prevent or minimize oxidative damage associated with several oxidative-stress-related diseases. The structural diversity of this class of compounds paved the way for drug discovery programs aimed at finding therapeutic agents. Attributes such as low-cost synthetic procedures, easy accessibility of reagents, and a broad spectrum of biological activities made sulfonamides and derivatives excellent candidates for synthesizing chemical libraries with structural diversity. Sulfonamide-based drugs are most of the sulfur-containing drugs approved by the United States Food and Drug Administration (FDA). Although sulfonamide derivatives have been extensively exploited as antibacterial agents, their therapeutic potential as antioxidants is relatively underexplored despite the prevalence of oxidative stress-mediated diseases and the urgent need for new and more effective antioxidant drugs. Some sulfonamide derivatives were shown to activate the nuclear factor erythroid 2-related factor 2 (Nrf2), the main regulator of the endogenous antioxidant response, a critical process used by cells in response to oxidative stress. The antioxidant role of sulfonamides and derivatives as Nrf2 activators is also reviewed. The antioxidant mechanism of action of sulfonamides has not been fully clarified, but as they have antioxidant properties, it is a subject worthy of in-depth study. The present review is focused on sulfonamides and derivatives as potential antioxidants along the period 2013-2021 and intends to stimulate research in the area.

18. Molecular mechanisms of ferroptosis and their involvement in brain diseases
Costa, I ; Barbosa, DJ ; Benfeito, S ; Silva, V ; Chavarria, D ; Borges, F ; Remiao, F ; Silva, R
in PHARMACOLOGY & THERAPEUTICS, 2023, ISSN: 0163-7258,  Volume: 244, 
Review,  Indexed in: crossref, scopus, wos 
Abstract Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxy-gen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxida-tion and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways.Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, pre-vent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting gluta-thione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, alpha-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors.Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of opportunities for novel therapeutic strategies and targets. Other stud-ies have shown a sensitivity of cancer cells with mutated RAS to ferroptosis induction and that chemotherapeutic agents and ferroptosis inducers synergize in tumor treatment. Thus, it is tempting to consider that ferroptosis may arise as a target mechanistic pathway for the treatment of brain tumors.Therefore, this work provides an up-to-date review on the molecular and cellular mechanisms of ferroptosis and their involvement in brain diseases. In addition, information on the main ferroptosis inducers and inhibitors and their molecular targets is also provided.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://

19. Drug discovery and amyotrophic lateral sclerosis: Emerging challenges and therapeutic opportunities
Soares, P ; Silva, C ; Chavarria, D ; Silva, FSG ; Oliveira, PJ ; Borges, F
in AGEING RESEARCH REVIEWS, 2023, ISSN: 1568-1637,  Volume: 83, 
Review,  Indexed in: crossref, wos 
Abstract Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons (MNs) leading to paralysis and, ultimately, death by respiratory failure 3-5 years after diagnosis. Edaravone and Riluzole, the only drugs currently approved for ALS treatment, only provide mild symptomatic relief to patients. Extraordinary progress in understanding the biology of ALS provided new grounds for drug discovery. Over the last two decades, mitochondria and oxidative stress (OS), iron metabolism and ferroptosis, and the major reg-ulators of hypoxia and inflammation - HIF and NF-kappa B - emerged as promising targets for ALS therapeutic intervention. In this review, we focused our attention on these targets to outline and discuss current advances in ALS drug development. Based on the challenges and the roadblocks, we believe that the rational design of multi -target ligands able to modulate the complex network of events behind the disease can provide effective therapies in a foreseeable future.

20. 8-Amide and 8-carbamate substitution patterns as modulators of 7-hydroxy-4-methylcoumarin?s antidepressant profile: Synthesis, biological evaluation and docking studies
Matos, MJ ; Novo, P ; Mayan, L ; Torres, I ; Uriarte, E ; Yanez, M ; Fontenla, JA ; Ortuso, F ; Alcaro, S ; Procopio, F ; Rodriguez Franco, MI ; Val, C ; Loza, MI ; Brea, J ; Borges, F ; Vina, D
in EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, ISSN: 0223-5234,  Volume: 248, 
Article,  Indexed in: crossref, scopus, wos 
Abstract Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC50 = 15.0 nM and IC50 = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t1/2 of 6.84 min, an intrinsic clearance of 195.63 mu L min-1 mg-1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depression.