Publications

Abstract Melanogenesis is a physiological pathway for the formation of melanin. Tyrosinase catalyzes the first step of this process and down-regulation of its activity is responsible for the inhibition of melanogenesis. The search for molecules capable of controlling hyperpigmentation is a trend topic in health and cosmetics. A series of heteroarylcoumarins have been synthesized and evaluated. Compounds 4 and 8 exhibited higher tyrosinase inhibitory activities (IC50 = 0.15 and 0.38 mu M, respectively), than the reference compound, kojic acid (IC50 = 17.9 mu M). Compound 4 acts as competitive, while compound 8 as uncompetitive inhibitor of mushroom tyrosinase. Furthermore, compounds 2 and 8 inhibited tyrosinase activity and melanin production in B16F10 cells. In addition, compounds 2-4 and 8 proved to have an interesting antioxidant profile in both ABTS and DPPH radicals scavenging assays. Docking experiments were carried out in order to study the interactions between these heteroarylcoumarins and mushroom tyrosinase.

Abstract Background: Virtual methodologies have become essential components of the drug discovery pipeline. Specifically, structure-based drug design methodologies exploit the 3D structure of molecular targets to discover new drug candidates through molecular docking. Recently, dual target ligands of the Adenosine A2A Receptor and Monoamine Oxidase B enzyme have been proposed as effective therapies for the treatment of Parkinson's disease. Methods: In this paper we propose a structure-based methodology, which is extensively validated, for the discovery of dual Adenosine A2A Receptor/Monoamine Oxidase B ligands. This methodology involves molecular docking studies against both receptors and the evaluation of different scoring functions fusion strategies for maximizing the initial virtual screening enrichment of known dual ligands. Results: The developed methodology provides high values of enrichment of known ligands, which outperform that of the individual scoring functions. At the same time, the obtained ensemble can be translated in a sequence of steps that should be followed to maximize the enrichment of dual target Adenosine A2A Receptor antagonists and Monoamine Oxidase B inhibitors. Conclusion: Information relative to docking scores to both targets have to be combined for achieving high dual ligands enrichment. Combining the rankings derived from different scoring functions proved to be a valuable strategy for improving the enrichment relative to single scoring function in virtual screening experiments.

Abstract This work aims to calculate the carbon footprint of the ICB produced by a Portuguese company and to compare it with other insulation materials available in the market. A Life Cycle Thinking approach and the ISO/TS 14067 (2013) requirements were followed in this work to perform a "cradle-to-gate" life cycle analysis. The inventory analysis mainly uses primary data collected from a Portuguese ICB producing company, complemented with secondary data from commercial life cycle databases and literature concerning respectively, the external transportation of the cork raw-material and the emission factors of electricity and fuel production and use. Results of this study show that ICB has a carbon footprint of 116.229 kg CO2 equivalent per m(3) of ICB. It is the only insulation material present in the market with a negative carbon footprint, which is mainly due to the utilization of cork, a renewable raw material, the proximity of its source to the factory, and the use of biomass for generating the steam needed for its production process. To the authors' knowledge, this is the first study to report the carbon footprint of ICB and to compare it with other building insulation materials.

Abstract Background: Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. Methods: We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. Results: The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. Conclusion: Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.

Abstract The effect of light-absorbing atmospheric particles on climate change has been incorporated into climate models, but the absence of brown carbon (BrC) in these models has been leading to significant differences between model predictions and measured data on radiative forcing. Also, little is known regarding the relationship between optical properties and chemical compositions of BrC. Thus, we have characterized the absorption properties of catechol and known heterogeneous ozonolysis products, with a theoretical approach based on density functional theory (DFT). While catechol presents a weak absorption maximum in the ultraviolet C (UVC) region, other polyaromatic derivatives present an absorption up to 6 times higher, with biphenyl-2,2',3,3'-tetraol, biphenyl-3,3',4,4',5,5'-hexaol, and terphenyl-2',3,3',3 '',4,4 ''-hexaol presenting the strongest absorption. Moreover, these derivatives now absorb in the ultraviolet B (UVB) and ultraviolet A (UVA) regions, which are types of actinic radiation in the ultraviolet (UV) region not filtered by atmosphere (contrary to UVC), with terphenyl molecules presenting the highest absorption maximum. Furthermore, the absorption efficiency of these compounds is potentiated in the condensed phase, such as cloud droplets, rain, fog, and water films, as a result of a higher degree of electron delocalization. This study provides reliable information regarding the absorption properties of BrC generated by catechol, which is essential for the development of accurate models of climate forcing.

Abstract O 2º Encontro de História para a Ciência no Ensino (2EHCE) foi uma organização conjunta da Universidade de Coimbra (UC), Universidade do Porto (UP) e Universidade de Trás-os-Montes e Alto Douro (UTAD) que teve lugar nos dias 26 e 27 de maio de 2017, no Departamento de Química da Universidade de Coimbra, integrando e dando continuidade ao III Colóquio de História da Ciência para o Ensino, na sequência da edição anterior realizado na UC em 2014. O Encontro teve associada uma Ação de Formação intitulada A História da Ciência no Ensino das Ciências, da responsabilidade do Gabinete de Formação da UTAD, creditada para os professores dos grupos 230, 510 e 520. Com o tema História da Ciência no Ensino do Século XXI, o 2EHCE visou juntar investigadores, professores e estudantes interessados na história e no ensino da Biologia, Geologia, Química, Física e Matemática, assim como das Ciências da Educação, Antropologia, Astronomia, Biologia Molecular, Bioquímica, Ecologia, Economia, Engenharias, Farmácia, Medicina, Nanociências, Psicologia, Sociologia, entre outras, num debate multicentrado e multidisciplinar. Para além de trabalhos focados no ensino, educação, didática e divulgação das ciências, o 2EHCE procurou congregar reflexões e estudos de carácter mais geral, disciplinares ou interdisciplinares, de história da cultura, da técnica e da indústria, assim como estudos epistemológicos, historiográficos, biográficos ou prosopográficos. Outros temas relevantes para a história da ciência e para o ensino, como sejam os estudos de género, o ensino das ciências em língua estrangeira e, de forma geral, as várias vertentes das interações entre as ciências, as tecnologias e as humanidades, foram muito bem-vindos para o espaço de diálogo que o 2EHCE procurou criar. No decurso do 2EHCE foram lembradas as memórias da Professora Celeste Gomes (1962-2016), docente do Departamento das Ciências da Terra da UC, que esteve na génese e organização dos encontros anteriores, e do Professor Sebastião Formosinho (1943-2016), docente do Departamento de Química da UC, que pertencia à Comissão Científica do Encontro. Durante os dois dias do 2EHCE foram apresentadas 58 comunicações orais e estiveram presentes 111 participantes oriundos de Portugal, Brasil e Espanha. Por último, gostaríamos de agradecer aos elementos da Comissão Científica, a todos os participantes, bem como às instituições que se associaram e que tornaram possível esta reunião científica.

Abstract Nanotechnology is one of the most innovative scientific research fields, especially with regard to medical applications. The use of nanotechnology in medical applications is called nanomedicine and is based on the application of nanoparticles for diagnosis and treatment of several clinical conditions. In particular, many physicochemically distinct nanomaterials have been tested in the form of nanoparticles for cancer diagnosis and therapy. This new branch of science, in which nanotechnology is used against cancer, has been named nanooncology. Nanooncology uses materials in nanoscale to delineate the tumor margins, to separate cancer cells from healthy cells, to identify micrometastasis, and to determine if the tumor has been completely removed or not. This approach means fewer side effects and less drug use. Nanoparticles also have the potential of site-specific targeting and controlled drug release; thus, a strong dose of drug could be concentrated within a specific area, but with a planned and scheduled release, to ensure maximum effectiveness and patient safety. Although being designed to target specific organs/tissues/cells, nanoparticles may interfere with other organs/tissues, such as liver and blood. Nanoparticles can be engineered to avoid the immune system recognition or to specifically inhibit or enhance the immune responses; they are strange bodies for the immune system and may induce undesirable immunotoxicity. This chapter highlights the benefits of nanotechnology and of nanomedicines for cancer diagnosis and therapy, focusing on the relevant aspects of nanotoxicology.

Abstract The aim of this study was the assessment of the physicochemical stability of D-alpha-tocopherol formulated in medium chain triglyceride nanoemulsions, stabilized with Tween(R)80 and Lipoid(R)S75 as surfactant and co-surfactant, respectively. D-alpha-tocopherol was selected as active ingredient because of its well-recognized interesting anti-oxidant properties (such as radical scavenger) for food and pharmaceutical industries. A series of nanoemulsions of mean droplet size below 90 nm (polydispersity index < 0.15) have been produced by high-pressure homogenization, and their surface electrical charge (zeta potential), pH, surface tension, osmolarity, and rheological behavior, were characterized as a function of the D-alpha-tocopherol loading. In vitro studies in Caco-2 cell lines confirmed the safety profile of the developed nanoemulsions with percentage of cell viability above 90% for all formulations. (C) 2016 The Authors.

Abstract Nanotechnology holds the promise of develop new processes for wastewater treatment. However, it is important to understand what the possible impacts on the environment of NMs. This study joins all the information available about the toxicity and ecotoxicity of NMs to human cell lines and to terrestrial and aquatic biota. Terrestrial species seems more protected, since effects are being recorded for concentrations higher than those that could be expected in the environment. The soil matrix is apparently trapping and filtering NMs. Further studies should focus more on indirect effects in biological communities rather than only on effects at the individual level. Aquatic biota, mainly from freshwater ecosystems, seemed to be at higher risk, since dose effect concentrations recorded were remarkable lower, at least for some NMs. The toxic effects recorded on different culture lines, also give rise to serious concerns regarding the potential effects on human health. However, few data exists about environmental concentrations to support the calculation of risks to ecosystems and humans.

Abstract Current advances in systems biology suggest a new change of paradigm reinforcing the holistic nature of the drug discovery process. According to the principles of systems biology, a simple drug perturbing a network of targets can trigger complex reactions. Therefore, it is possible to connect initial events with final outcomes and consequently prioritize those events, leading to a desired effect. Here, we introduce a new concept, 'Systemic Chemogenomics/Quantitative Structure-Activity Relationship (QSAR)'. To elaborate on the concept, relevant information surrounding it is addressed. The concept is challenged by implementing a systemic QSAR approach for phenotypic virtual screening (VS) of candidate ligands acting as neuroprotective agents in Parkinson's disease (PD). The results support the suitability of the approach for the phenotypic prioritization of drug candidates.