Percorrer por autor "Calhelha, Ricardo C."
A mostrar 1 - 10 de 533
Resultados por página
Opções de ordenação
- 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 VEGFR-2 tyrosine kinase inhibitors: Synthesis, biological evaluation, and molecular modelling studiesPublication . Soares, Pedro; Costa, Raquel; Froufe, Hugo J.C.; Calhelha, Ricardo C.; Peixoto, Daniela; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Soares, Raquel; Queiroz, Maria João R.P.The Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) is a tyrosine kinase receptor involved in the growth and differentiation of endothelial cells that is implicated in tumor-associated angiogenesis. In this study novel 1-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas were synthesized and evaluated for the VEGFR-2 tyrosine kinase inhibition. Three of these compounds showed good VEGFR-2 inhibition presenting low IC50 values (150-199 nM) in enzymatic assays. The latter promoted also significant inhibition of cell proliferation at low concentrations (0.5-1 µM), not affecting cell viability, of VEGF-stimulated Human Umbilical Vein Endothelial Cells (HUVECs) using the BrdU assay. The determination of the total and phosphorylated (active) VEGFR-2 was performed by western-blot, and it was possible to conclude that the compounds significantly inhibit the phosphorylation of the receptor at 1 µM pointing to their antiproliferative mechanism of action in HUVECs. The molecular rationale for inhibiting the tyrosine kinase domain of VEGFR-2 was also done and discussed using molecular docking studies.
- 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.
- Actividade antifúngica de extractos fenólicos do mel de Trás-os-MontesPublication . Barros, Susana; Calhelha, Ricardo C.; Estevinho, Leticia M.O mel é considerado um produto alimentar benéfico e promotor de saúde, através da prevenção de doenças. Estas propriedades devem-se em parte a presença de compostos fenólicos (ácidos fenólicos e flavonóides) na sua composição.
- Actividade antimicrobiana de cogumelos silvestres comestíveis: Lactarius deliciosus, Sarcodon imbricatus e Tricholoma portentosumPublication . Barros, Lillian; Calhelha, Ricardo C.; Vaz, Josiana A.; Ferreira, Isabel C.F.R.; Baptista, Paula; Estevinho, Leticia M.Actualmente a prevalência de doenças infecciosas é um problema à escala mundial, exigindo uma intensa pesquisa de novos agentes antimicrobianos activos contra microrganismos patogénicos. A introdução de produtos naturais para este fim tem suscitado muito interesse nos últimos anos. Os cogumelos para além de reconhecido valor nutricional possuem benefícios medicinais, nomeadamente no tratamento contra cancro de estômago, esófago e pulmões. Tanto o corpo frutificante como o micélio contem compostos com actividade anti bacteriana e antifúngica.
- Actividade antimicrobiana de cogumelos silvestres comestíveis: Lactarius deliciosus, Sarcodon imbricatus e Tricholoma portentosumPublication . Barros, Lillian; Calhelha, Ricardo C.; Vaz, Josiana A.; Ferreira, Isabel C.F.R.; Baptista, Paula; Estevinho, Leticia M.Actualmente a prevalência de doenças infecciosas é um problema à escala mundial, exigindo uma maior investigação de novos agentes antimicrobianos activos contra microorganismos patogénicos, Portanto a pesquisa de novos produtos com propriedades antimicrobianas tem-se tornado um grande domínio.
- Acute Effects of Nitrate-Rich Beetroot Juice on Cardiovascular and Hemodynamic Responses to Flywheel Resistance Exercise: A Randomized, Double-Blind, Placebo-Controlled Crossover TrialPublication . Primo, Mateus Chaves; Viana, Ítalo Santiago Alves; Goulart-Silva, Leonardo Silveira; Machado, Wanderson Matheus Lopes; Leite , Luciano Bernardes; Forte, Pedro; Calhelha, Ricardo C.; Monteiro, António M.; Branquinho, Luís; Silva, Sandro Fernandes; Oliveira, Claudia Eliza Patrocínio de; Moreira, Osvaldo CostaBeetroot juice is a popular nutritional resource in sports due to its ergogenic effects, promoting vasodilation, hypotension, improved energy efficiency, and reduced oxygen cost. However, its role in modulating the autonomic nervous system during strength training remains understudied. This study assessed the effects of acute nitrate-rich beetroot juice supplementation on cardiovascular and hemodynamic responses to flywheel resistance exercise. Fifteen male participants (age 22 +/- 3.64 years) from the Federal University of Vi & ccedil;osa completed a crossover, double-blind, placebo-controlled trial. Each participant consumed either 400 mg of standardized nitrate or a placebo before performing 4 sets of 8-12 repetitions at 100% of their maximum concentric strength using a leg extension exercise, with 90 s recovery intervals. Heart rate, blood pressure, oxygen saturation, and subjective perception of effort were measured after each set. Data were analyzed using SPSS 23, employing the Shapiro-Wilk normality test, t-test for related samples, and MANOVA with time and supplement factors. NO3- supplementation led to a smaller increase in systolic blood pressure (SBP) during exercise compared to the placebo and reduced diastolic blood pressure (DBP) in the last set, reflecting decreased peripheral vascular resistance. However, no significant effects were observed for heart rate, rate-pressure product, oxygen saturation, time under tension, or subjective perception of effort. These findings suggest that NO3- supplementation can offer cardiovascular benefits by attenuating blood pressure increases during strength training, highlighting its potential as a low-risk ergogenic aid for healthy young men.
- Adansonia digitata L. (mukua): um possível alimento funcionalPublication . Fernandes, Filipa Alexandra; Carocho, Márcio; Calhelha, Ricardo C.; Pires, Tânia C.S.; Freitas, José Carlos; Prieto Lage, Miguel A.; Heleno, Sandrina A.; Barros, LillianAdansonia digitata L. é espécie africana com vários usos tradicionais, nomeadamente medicinal e alimentar [1,2]. A polpa do seu fruto, comumente conhecido como mukua, está aprovada como um ingrediente alimentar pela Comissão Europeia e pela “Food and Drug Administration of the United States of America” [1]. Assim o objetivo deste trabalho foi comprovar a potencialidade da polpa da mukua como um alimento funcional através da sua caracterização nutricional, mineral e bioativa. O perfil nutricional foi obtido aplicando metodologias oficiais de análise AOAC [3]. O conteúdo mineral foi determinado por espectrofotometria de absorção atómica e o potencial bioativo foi determinado através da atividade antioxidante pelo ensaio antioxidante celular (CAA) e um ensaio de inibição de substâncias reativas do ácido tiobarbitúrico (TBARS). Além disso, a atividade antimicrobiana foi também determinada, através do método de microdiluição, e a atividade antitumoral foi avaliada em três linhas celulares tumorais humanas: adenocarcinoma gástrico (AGS), carcinoma de mama (MCF-7), células de carcinoma de pulmão (NCI-H460), e a citotoxicidade em culturas de células não tumorais de rim de macaco africano (VERO), através do ensaio da Sulforrodamina B. Relativamente aos resultados obtidos, a polpa de mukua apresentou um teor de humidade muito baixo (11,9 + 0,3 g/100 g ms). Os macronutrientes presentes em maior quantidade foram os hidratos de carbono (89,6 ± 0,2 g/100 g ms), seguidos das proteínas (2,7 ± 0,3 g/100 g ms) e da gordura bruta (1,8 + 0,1 g/100 g ms), representando um valor energético de 386 ± 1 kcal/100 g ms. Quanto ao perfil mineral, a amostra revelou um alto teor em potássio (20,4 ± 0,8 g/100 g ms), estando também presentes minerais como o magnésio (3,28 ± 0,08 g/100 g ms), o cálcio (2,79 ± 0,07 g/100 g ms), o manganês (2,02 ± 0,09 g/100 g ms) e o ferro (1,53 ± 0,09 g/100 g ms). Em relação à atividade antioxidante, a polpa inibiu cerca de 32% da oxidação celular no método CAA e exibiu um valor de EC50 de 23,0 ± 0,1 μg/mL no ensaio de TBARS. Para a atividade antimicrobiana, a polpa apresentou atividade bacteriostática contra a maioria das bactérias testadas. No ensaio de citotoxicidade, a polpa demonstra capacidade de inibir a proliferação celular contra as linhas tumorais testadas, principalmente contra AGS com valores de GI50 de 92 ± 1 μg/mL, sem toxicidade para as células não-tumorais. Este estudo mostra que a polpa de mukua, além de ser nutricionalmente interessante, possui alto teor em minerais, nomeadamente em potássio que é um composto essencial para a bom funcionamento do corpo, estando associado à prevenção de doenças como diabetes, osteoporose e ainda doenças cardiovasculares. Além disso, a polpa da mukua possui alto potencial bioativo, o que indica que o seu consumo pode oferecer benefícios para a saúde, tornando-o num potencial alimento funcional.
- Aesculus hippocastanum L.: a simple ornamental plant or a source of compelling molecules for industry?Publication . Dridi, Asma; Reis, Filipa S.; Pires, Tânia C.S.P.; Calhelha, Ricardo C.; Pereira, Carla; Zaghdoudi, Khalil; Ferreira, Isabel C.F.R.; Barros, Lillian; Barreira, João C.M.Aesculus hippocastanum L., also known as horse chestnut, is an ornamental tree whose seeds are mostly discarded in landfills in the regions where they are grown. However, recent studies have shown that these seeds can be a source of interesting compounds for several industries. This work aimed to chemically characterize horse chestnut seeds at the level of compounds recognized for their wide bioactivity, i.e., organic acids, including phenolic compounds, using chromatographic methodologies (UFLC-DAD and LC-DAD-ESI/MSn). In addition, the bioactivity of these seeds was evaluated by in vitro methodologies, seeking to relate the respective (bio)activity to the compounds present in the endocarp (husk), seed coat (skin), and peeled seed (pulp). The antioxidant activity (lipid peroxidation inhibition and oxidative haemolysis inhibition), antibacterial potential (against Gram-positive and Gram-negative bacteria) and cytotoxicity (in human tumour cell lines and porcine liver primary cells) were evaluated. Kaempferol-O-pentoside-O-hexoside-O-hexoside was the main phenolic identified in the pulp. At the same time, (-)-epicatechin and beta-type (epi)catechin dimer were the major phenolics present in husk and skin, respectively. In general, A. hippocastanum extracts presented antioxidant and antibacterial potential, without toxicity up to the maximal tested dose. Overall, these findings anticipate potential applications of A. hippocastanum seeds in food- or pharmaceutical-related uses.
- Agaricus blazei Murril - a potential ingredient for nutraceutical outcomesPublication . Taofiq, Oludemi; Rodrigues, Francisca; Barros, Lillian; Calhelha, Ricardo C.; González-Paramás, Ana María; Barreiro, M.F.; Oliveira, Beatriz; Ferreira, Isabel C.F.R.The concept of bio-economy has emerged to overcome some sustainability challenges, and this involves conversion of agricultural residues and waste streams into high value-added products that can be utilized as ingredients for several bio-based industrial processes, delivering both economic growth, scientific interest and a better environment. The present work was carried out to re-utilize discarded Agaricus blazei Murill. Its nutritional composition was evaluated and ethanolic extracts were prepared by Soxhlet extraction to be further evaluated for their anti-inflammatory, anti-tyrosinase and cytotoxic properties against different tumor cell lines (SRB assay). MTT and LDH assays were also used to determine cell viability and cell death respectively in Caco-2 and HT29 cells lines. Essential nutrients such as carbohydrates, proteins and fat, were found; twenty fatty acids were detected, sugars (mannitol and trehalose), α-tocopherol and oxalic acid were also present. The extracts, up to 100 μg/mL, were able to maintain viability of Caco-2 and HT29 cells. The extracts also presented anti-tyrosinase activity (EC50 1.33±0.02 mg/mL) and with no toxicity in tumor cells. The results obtained suggested that the extracts obtained from Agaricus blazei Murill residues can be utilized as an inexpensive and sustainable source of nutraceutical and functional food ingredients.