CIMO - Resumos em Proceedings Não Indexados à WoS/Scopus
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Browsing CIMO - Resumos em Proceedings Não Indexados à WoS/Scopus by Author "Abreu, Rui M.V."
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- 1-aryl-3-(4-(7-methylthieno[3,2-d]pyrimidin-4-yloxy)phenyl)ureas: synthesis and molecular modelling studies using VEGFR-2Publication . Soares, Pedro; Froufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Borges, Fernanda; Queiroz, Maria João R.P.The development of anticancer drugs inhibiting angiogenesis has been an area of extensive research in the past decade. Angiogenesis is a requirement for tumor growth and metastasis and occurs through several signalling pathways. One key pathway that initiates proliferation and migration of endothelial cells is signalling through the vascular endothelial growth factor receptor-2 (VEGFR-2).1 Therefore, small molecules that block this signalling pathway through inhibition of VEGFR-2 tyrosine kinase activity could potentially inhibit angiogenesis and tumor growth. Recently works describing thienopyrimidine2 and thienopyrimidine 1,3-diarylureas3 as VEGFR-2 inhibitors have emerged in the literature. Here we present the synthesis of new 1-aryl-3-(4-(7-methylthieno[3,2-d]pyrimidin-4-yloxy)phenyl)ureas 2 in high yields by reaction of 4-[(7-methylthieno[3,2-d]pyridin-4-yl)oxy]aniline 1 with arylisocyanates. The former was prepared by regioselective nucleophilic substitution of 4-chloro-7-methylthieno[3,2-d]pyrimidine with 4-aminophenol
- 1-Aryl-3-[ 4-( thieno[3,2-d]pyrimidin-4-yloxy )phenyl]ureas as VEG FR2 inhibitors: synthesis, docking enzymatic and cellular assaysPublication . Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Abreu, Rui M.V.; Froufe, Hugo J.C.; Ferreira, Isabel C.F.R.; Costa, Raquel; Soares, Raquel; Queiroz, Maria João R.P.A number of thienopyrimidines derivatives have shown potent VEGFR2 (Vascular Endothelium Growth Factor Receptor2) tyrosine kinase inhibition activity.[ll VEGF is a sun·ogate marker of angiogenesis that activates VEGFR2 in endothelial cells. Here we present the synthesis of new 1-aryl-3-[ 4-(thieno[3,2-d]pyrimidin-4- yloxy)phenyl]ureas from the aminodi(hetero)arylether 1, also prepared by us, which was reacted with arylisocyanates to give the corresponding 1,3-diarylureas 2a-c.
- 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as potential inhibitors of VEGFR-2: synthesis and molecular modelling studiesPublication . Soares, Pedro; Froufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Borges, Fernanda; Queiroz, Maria João R.P.Angiogenesis is a requirement for tumor growth and metastasis and occurs through several signalling pathways. One key pathway that initiates proliferation and migration of endothelial cells is signalling through the vascular endothelial growth factor receptor-2 (VEGFR-2).1 Therefore, small molecules that block this signalling pathway through inhibition of the VEGFR tyrosine kinase activity could potentially inhibit angiogenesis and tumour growth. Recently works describing thienopyrimidines2 and thienopyridine ureas3 as inhibitors of VEGFR-2 have appeared in the literature. Here we present the synthesis of new 1,3-diarylureas 2 starting by regioselective nucleophilic substitution of the 4-chlorothieno[3,2-d]pyrimidine with 4-aminophenol to obtain 4-(thieno[3,2-d]pyridin-4-yloxy)aniline 1 which reacts with different arylisocyanates
- 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR2 tyrosine kinase inhibitors: synthesis, docking studies, enzymatic and cellular assaysPublication . Queiroz, Maria João R.P.; Peixoto, Daniela; Soares, Pedro; Abreu, Rui M.V.; Froufe, Hugo J.C.; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Costa, Raquel; Soares, RaquelA number of thienopyrimidines derivatives have shown potent vascular endothelial growth factor receptor 2 (VEGFR2) inhibition activity. Here, we present the synthesis of new 1-aryl-3-[4-(thieno[3,2-d) pyrimidin-4-yloxy)phenyl]ureas by promoting t he regioselective attack of the hydroxy group of the 4-aminophenol in the chlorine nucleophilic displacement on two 4-chlorinated thieno[3,2-d]pyrimidines, obtaining compounds la and 1b which were reacted with arylisocyanates to give t he corresponding 1,3-diarylureas 2a-f (see scheme). These compounds were evaluated for inhibition of VEGFR2 tyrosine kinase activity using enzymatic assays, and 2a- c showed good inhibition ability with IC50 values in the range of hundreds of nanomolar. The rationale for the inhibition activity is also discussed using docking. To examine the activity of 2a- c in endothelial cells, human umbilical vein endothelial cells (HUVECs) were cultured in the presence or absence of each compound in different concentrations. A decrease in the proliferation of HUVECs was observed by the incorporation of BrdU quantified by ELISA assay. Given the established role of VEGFR2 in proliferation and migration of endothelial cells, these molecules are promising antiangiogenic agents that can be used for therapeutic purposes in pathological conditions where angiogenesis is exacerbated, such as cancer.
- A amilóide A no leite é útil no diagnóstico de mastites subclínicas em caprinos?Publication . Quintas, Helder; Sequeira, Ana; Coelho, Ana Cláudia; Abreu, Rui M.V.; Alegria, Nuno; Mendonça, ÁlvaroAs mastites são responsáveis por perdas económicas extremamente elevadas nos ruminantes leiteiros e, deste ponto de vista, a forma subclínica é a mais preocupante. Assim, o diagnóstico realizado de forma precoce e eficaz torna-se numa das medidas mais importantes no controlo desta doença. A mensuração das proteínas da fase aguda da inflamação (PFA), para deteção de mastites, tem sido alvo de várias pesquisas em bovinos e diversos estudos comprovam um incremento na produção de haptoglobina e Amilóide A (AA) séricas em vacas com mastites clínicas e subclínicas. Apesar da reduzida literatura disponível em pequenos ruminantes, a Amilóide A sérica está indicada como a PFA mais sensível em ovinos. Recentemente foi descoberta uma isoforma específica de AA no leite de bovinos e ovinos, denominada por Amilóide A do leite. Esta é produzida pelas células epiteliais e aumenta precocemente em situações de mastite. No presente estudo foi avaliada a utilidade do doseamento de Amilóide A do leite, através de um ensaio imunoenzimático, no diagnóstico de mastites em caprinos. Semanalmente, durante seis semanas consecutivas, foram recolhidas amostras de leite de 12 cabras de raça Serrana, de manhã, antes de se proceder à ordenha. No total foram recolhidas 144 amostras de metades mamárias. Com base nos resultados microbiológicos e da contagem de células somáticas, as metades mamárias foram divididas em 4 grupos: saudáveis, com mastites subclínicas e com mastites subclínicas duvidosas – latentes e inespecíficas. Os resultados das concentrações de Amilóide A do leite mostraram diferenças significativas (P<0,05) entre as metades mamárias saudáveis e as com mastites subclínicas e entre o grupo com mastites subclínicas inespecíficas e os restantes grupos. O doseamento da Amilóide A do leite revelou-se uma técnica útil na diferenciação das metades mamárias saudáveis das com mastites subclínicas. Porém, esta distinção foi condicionada pelas mastites subclínicas inespecíficas.
- Anti-inflammatory activity of mushrooms extracts, identified phenolic acids and their possible metabolitesPublication . Taofiq, Oludemi; Calhelha, Ricardo C.; Heleno, Sandrina A.; Barros, Lillian; Martins, Anabela; Abreu, Rui M.V.; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.Mushrooms are rich sources of many bioactive compounds, such as phenolic acids, that play an important role in the organism, acting as antioxidants, antitumors, antimicrobials, immunomodulators, among others. However, their anti-inflammatory activity has not been deeply studied. In the present study, the ethanolic extracts of fourteen edible mushroom species were firstly characterized in terms of phenolic acids and related compounds by HPLC-PDA, followed by the study of the anti-inflammatory activity of those extracts and corresponding identified compounds, by using LPS (lipopolysaccharide) activated RAW 264.7 macrophages and measuring the inhibition in NO production. Furthermore, methylated and glucuronated derivatives of the identified compounds (p-hydroxybenzoic, p-coumaric and cinnamic acids) were synthesised and evaluated for the same bioactivity to understand the contribution of these compounds for the overall activity of the extracts, and to establish structure-activity relationships. Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential, presenting also the highest concentration in cinnamic acid, which was also the individual compound displaying the highest activity. The derivative compounds of p-coumaric acid revealed the strongest properties, especially the compound CoA-M1 (presenting an ester instead of the carboxylic group), that exhibited a very similar activity to the one showed by dexamethasone, used as anti-inflammatory standard. On the contrary, p-hydroxybenzoic acid derivatives revealed the lowest activity. Overall, the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity; nevertheless, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.
- Anti-proliferative activity of thieno[3,2-b]pyridine derivatives in tumoral and primary hepatic cell lines.Publication . Abreu, Rui M.V.; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.; Adega, Filomena; Chaves, Raquel
- Antioxidant and anti-inflammatory properties of red, white and pink globe amaranth hydromethanolic extractsPublication . Liberal, Ângela; Pereira, Carla; Calhelha, Ricardo C.; Abreu, Rui M.V.; Adega, Filomena; Ferreira, Isabel C.F.R.Medicinal plants have been playing a vital role on human health and healing, representing one of the major sources of drugs in modem and traditional medicine [1]. Plants synthesize and preserve a variety of biochemical products that can be used as pharmaceutical compounds [2], and recently there has been an increasing interest in the therapeutic potential of plants as antioxidants and anti-inflammatories [3]. Oxidative stress and inflammation play critical roles in the pathogenesis of many diseases, such as cancer, cardiovascular disease, arthritis and obesity [4], among others. Thus, the aim of this study was to explore the bioactivity of red, white and pink globe amaranth (different cultivars of Gomphrena globosa L.) hydromethanolic extracts, namely the antioxidant and anti-inflammatory activities. The antioxidant activity was tested through radicals scavenging capacity, reducing power, and lipid peroxidation inhibition, whereas the anti-inflammatory activity was assessed by monitoring the inhibition of nitric oxide (NO) release in the mouse macrophage-like cell line RAW 264.7. The absence of toxicity of the extracts was also confirmed by the sulphorodamine B (SRB) assay applied to a porcine liver primary culture (PLP2) established by the authors. Among the three studied samples, pink globe amaranth showed the highest antioxidant activity, with the lowest ECso values (0.25 to 1.02 mg/mL), followed by red (0.41 to 1.30 mg/mL) and white (0.57 to 1.47 mg/mL) globe amaranth. Regarding the anti-inflammatory activity, pink and red globe amaranth also revealed the lowest ECso values (133 and 136 pg/mL, respectively), with white globe amaranth revealing an ECso value of 198pg/mL. None of the extracts presented cytotoxicity in PLP2 cells up to 400 pg/mL. From the results obtained, we can conclude that the extracts of these plants can be considered good sources of antioxidants and can also be used for anti-inflammatory purposes.
- Aplicação de ferramentas de quimioinformática no desenvolvimento de novos fármacos: tienopiridinas como inibidores de VEGFR-2Publication . Abreu, Rui M.V.; Froufe, Hugo J.C.; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.A quimioinformática é uma área científica que utiliza métodos computacionais para resolver problemas de Química normalmente associados à representação virtual da estrutura de compostos químicos, quer sejam sintéticos ou naturais. t: provavelmente a disciplina de computação aplicada com maior historial, embora o termo quimioinformática só tenha surgido há menos de uma década. As ferramentas computacionais utilizadas na quimioinformática têm tido um enorme impacto no desenvolvimento de novos fármacos bem como na área ambiental para a estimativa de toxicidade de produtos químicos existentes no mercado (1 ). As temáticas mais importantes desta área incluem a representação de estruturas de compostos químicos e o uso dessas representações na pesquisa por similaridade em bases de dados de estruturas ou de reações químicas. Também a criação, manutenção, acesso e exploração de grandes bases de dados envolvendo estruturas moleculares é um tópico muito importante na quimioinformática. Outras aplicações incluem estudos de modelação molecular, com a utilização de técnicas computacionais avançadas de "molecular docking" e "molecular dynamics" para o estudo de compostos químicos como potenciais inibidores de proteínas associadas a diferentes patologias (2); bem como estudos QSAR (Quantitative Structure-Activity Relashionships) e aplicação de técnicas de data mining para a extração de informação importante sobre uma determinada bioatividade de um composto químico. Neste sessão vamos utilizar ferramentas computacionais para analisar e manipular estruturas de compostos químicos bem como fazer um estudo da interação de um composto com uma determinada proteína alvo. Vamos demostrar como estas ferramentas podem ser utilizadas para o desenvolvimento de novos fármacos antitumorais. Como exemplos vamos utilizar compostos derivados de tienopiridinas, que estão a ser desenvolvidos no âmbito de um projeto de investigação em curso e que tem como objetivo o desenvolvimento de novos inibidores da proteína tirosina cinase VEGFR-2 (Vascular Endothelial Growth Factor Receptor).
- Basil and eucalyptus as a source of essential oils with bioactive propertiesPublication . Pereira, Eliana; Caleja, Cristina; Sprea, Rafael M.; Abreu, Rui M.V.; Pires, Tânia C.S.; Amaral, Joana S.; Prieto Lage, Miguel A.; Barros, LillianAromatic and medicinal plants have been used worldwide for culinary purposes aiming to modify, enhance or improve the flavour of foods. In addition, several aromatic plants are also recognized for their empiric use in folk medicine due to their beneficial health effects1. The secondary metabolites of aromatic plants could have diverse applications in industry, and several essential oils have a Generally Recognized as Safe (GRAS) status attributed by the Food and Drug Administration (FDA). Currently, these natural matrices have been characterized by having active antioxidant components in their composition that have a direct impact on food quality and have potential benefits on human health2. In addition, studies focusing on different aromatic plants have suggested the use of their essential oils and some constituents as promising alternatives for obtaining natural preservatives. The present work reports a study on the bioactivity of essential oils obtained from two species of aromatic plants: Ocimum basilicum L. (basil) and Eucalyptus globulus Labill. (eucalyptus). The essential oil was obtained by hydrodistillation using a Clevenger apparatus and volatile compounds were analyzed by GC-MS equipped with DB-5MS fused-silica column. The antimicrobial activity was determined by broth microdilution assay against several Gram-positive and Gram-negative ATCC bacterial strains, and fungi. The bioactive potential was evaluated through several in vitro assays, namely antioxidant activity using two different assays: DPPH (2,2-diphenyl-1- picrylhydrazyl) radical scavenging activity and reducing power; cytotoxic activity using three tumour cell-lines: CaCo (colorectal adenocarcinoma), MCF-7 (breast adenocarcinoma) and NCIH460 (non-small cell lung carcinoma) and a non-tumor cell line of monkey kidney (VERO), by applying the sulforhodamine B assay; anti-inflammatory activity was assessed using RAW 264.7 macrophage cells. In general, the results revealed a auspicious antimicrobial potential of the essential oils against the tested strains, as well as a very promising antioxidant and anti-inflammatory activities. In addition, it was also possible to verify the absence of toxicity of both extracts. Therefore, essential oils extracted from the studied plants can be appealing alternatives to the currently used synthetic additives, with potential application in the food and pharmaceutical industries for their relevant bioactive properties.