Showing: 10 from total: 2609 publications
261. The mitochondria-targeted antioxidant AntiOxCIN4 protects against cardiac oxidative/nitrosative stress in the amyotrophic lateral sclerosis SOD1G93A mouse
Mena, D ; Cagide, F ; Soares, P ; Grilo, L ; Pinheiro, P ; Teixeira, J ; Borges, F ; Oliveira, PJ ; Duarte, AI
in EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2023, ISSN: 0014-2972,  Volume: 53, 
Abstract,  Indexed in: wos 

262. The mitochondria-targeted antioxidant AntiOxCIN4 attenuates brain and skeletal muscle oxidative/nitrosative stress in the amyotrophic lateral sclerosis SOD1G93A mouse
Mena, D ; Soares, P ; Cagide, F ; Grilo, L ; Silva, DF ; Pinheiro, P ; Ferreiro, E ; Teixeira, J ; Silva, F ; Borges, F ; Oliveira, PJ ; Duarte, AI
in EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2023, ISSN: 0014-2972,  Volume: 53, 
Abstract,  Indexed in: wos 

263. Annealing-assisted optimization for persistency of afterglow of SrAl2O4:Eu2+/Dy3+ microparticles for forensic detection
Kumar, A ; Crista, DMA ; Núñez-Montenegro, A ; da Silva, JCGE ; Verma, SK
in RSC ADVANCES, 2023, ISSN: 2046-2069,  Volume: 13, 
Article,  Indexed in: crossref, wos, scopus 
Abstract In the present work, Eu2+/Dy3+ ions doped/co-doped into persistent SrAl2O4 microparticles have been developed through solid-state synthesis followed by homogenization and particle size reduction in a ball milling device. These particles have shown a broad and long-persistent afterglow around the 528 nm wavelength of electromagnetic radiation through a broad excitation at around 400 nm. The luminescence intensity was optimized through the selection of different annealing temperatures in the range of 1100 C-degrees to 1500 C-degrees, with intervals of 100 C-degrees. Several structural and optical characterization techniques, such as XRD, SEM, FTIR, thermogravimetric analysis, and photoluminescence, were utilized to judge the preparation and ability of these particles in possible applications in latent fingermark detection on various difficult surfaces. The persistency and stability of these particles were calculated using a digital lux meter.

264. 2H-chromene and 7H-furo-chromene derivatives selectively inhibit tumour associated human carbonic anhydrase IX and XII isoforms
Sequeira, L ; Distinto, S ; Meleddu, R ; Gaspari, M ; Angeli, A ; Cottiglia, F ; Secci, D ; Onali, A ; Sanna, E ; Borges, F ; Uriarte, E ; Alcaro, S ; Supuran, CT ; Maccioni, E
in JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2023, ISSN: 1475-6366,  Volume: 38, 
Article,  Indexed in: crossref, scopus, wos 
Abstract Tumour associated carbonic anhydrases (CAs) IX and XII have been recognised as potential targets for the treatment of hypoxic tumours. Therefore, considering the high pharmacological potential of the chromene scaffold as selective ligand of the IX and XII isoforms, two libraries of compounds, namely 2H-chromene and 7H-furo-chromene derivatives, with diverse substitution patterns were designed and synthesised. The structure of the newly synthesised compounds was characterised and their inhibitory potency and selectivity towards human CA off target isoforms I, II and cancer-associated CA isoforms IX and XII were evaluated. Most of the compounds inhibit CA isoforms IX and XII with no activity against the I and II isozymes. Thus, while the potency was influenced by the substitution pattern along the chromene scaffold, the selectivity was conserved along the series, confirming the high potential of both 2H-chromene and 7H-furo-chromene scaffolds for the design of isozyme selective inhibitors. [GRAPHICS]

265. 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] .

266. Propargylamine: an important moiety in drug discovery
Carneiro, A ; Uriarte, E ; 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.

267. Sulfonamide a Valid Scaffold for Antioxidant Drug Development
Egbujor, MC ; Garrido, J ; 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.

268. 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:// creativecommons.org/licenses/by-nc-nd/4.0/).

269. Legal, financial and fiscal measures to support the collection solutions of biowaste in Portugal
David, F ; Rodrigues, PM ; Soares, E ; Azevedo, TC
in Taking on Climate Change Through Green Taxation, 2023, ISSN: 2475-6644, 
Book Chapter,  Indexed in: crossref, scopus 
Abstract The Portuguese Decree-Law No. 102-D/2020, of December 10 (PCM, 2020b), dictates the implementation of biowaste selective collection networks or the separation and recycling of biowaste at the source until December 31, 2023. This chapter aims to analyze the financial support provided to municipalities (local authorities) for implementing biowaste collection solutions, such as on public roads or through door-to-door collection, and to citizens for adopting biowaste separation and recycling practices through domestic or community composting. The authors also explore the application of the polluter-pays principle, which requires citizens to pay environmental taxes and fees to support sustainable development. Regarding this focus, the chapter highlights the legal, financial, and fiscal measures used to support biowaste collection and recycling efforts in Portugal, providing insight into the steps needed to achieve a sustainable environment while addressing the economic and social needs of the population. © 2023, IGI Global.

270. 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, scopus, 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.