570 research outputs found

    Synthesis of Tetracyclic systems and (Thio)Ureas from Aminodi(Hetero)Arylamines in the Thieno[3,2-b]Pyridine series

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    Foundation for the Science and Technology (FCT–Portugal) for financial support through the Portuguese NMR network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research centre PEst-C/QUI/UI686/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-doctoral grant of R.C.C. SFRH/BPD/68344/2010

    Mathematical models of cytotoxic effects in endpoint tumor cell line assays: Critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats

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    The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98.The authors are grateful to the Foundation for Science and Technology (FCT) of Portugal and FEDER for financial support to CIMO (UID/AGR/00690/2013); and to the Xunta de Galicia for financial support for the post-doctoral research of M. A. Prieto.info:eu-repo/semantics/publishedVersio

    Radical scavenging activity, lipid peroxidation inhibition and redox profile of aminodiarylamines in the thieno[3,2-b]pyridine series

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    The reducing properties of diarylamines make them very important as antioxidants, especially as radical scavengers as it has been demonstrated by our and other research groups [1 -3]. Three di(hetero)arylamines were prepared by C- N coupling of the methyl3-amino-6-bromothieno(3,2- b]pyridine-2-carboxylate with bromonitrobenzenes and further reduced to the amino compounds 1a-c (Scheme) (4].FCT for financial support through the NMR Portuguese network (Bruker 400 Avance 111-Univ Minho). To FCT and FEDER-COMPETE/QREN/EU for financial support through the research unities PEstC/ QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011 , the research project PTDC/QUI-QUI/111 060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/SPD/68344/201 0) also financed by POPH and FSE

    Toxicity effects of fungicide residues on the wine-producing process

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    We report the detection of several fungicide residues (Dichlofluanid, Benomyl, Iprodione, Procymidone and Vinclozolin) in red and white bottled wines from two Portuguese wine-producing zones. Studies were done in order to evaluate the active compound transfer percentage from grapes to the final product along fermentation process. We also investigated their effects in Saccharomyces and non-Saccharomyces yeasts as well as their influence on the physical, chemical and organoleptic wine properties. All the tested fungicides had a negative effect on in vitro yeast growth, with Dichlofluanid and Benomyl being the most toxic. Zygosaccharomyces rouxii and Saccharomyces cerevisiae were the most resistant yeasts while Rhodotorula glutinis was the most susceptible. Microvinification experiments carried out in the presence of fungicides produced wine samples with unaltered physical, chemical and organoleptic properties, though Benomyl, a slight delay in the initiation of fermentation process was observed

    Chemical characterization and bioactive properties of bee venom samples from Northeast of Portugal

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    O veneno de abelha (VA) ou apitoxina é um produto apícola que tem sido utilizado desde os tempos ancestrais para múltiplas finalidades, nomeadamente em medicina tradicional na apiterapia. Trata -se de uma mistura complexa de substâncias que lhe conferem propriedades bioativas. No presente trabalho, analisaram -se cinco amostras de VA obtidas a partir de Apis mellifera iberiensis de dois apiários diferentes (Aveleda e Milhão, na região de Bragança). Foram, caracterizadas quimicamente e avaliadas quanto às suas propriedades antioxidantes, anti -inflamatórias e citotóxicas. A análise das amostras por LC -DAD -ESI/MSn demonstrou que a melitina (MEL) era o composto maioritário, seguido da fosfolipase A2 (PLA2) e da apamina (APA). Todas as amostras demonstraram atividade antioxidante, medida pela capacidade captadora de radicais livres, poder redutor e inibição da peroxidação lipídica, e anti -inflamatória, determinada pela capacidade de diminuir a formação de NO em macrófagos de rato (RAW 264,7). No entanto, não foi observada uma relação direta entre as propriedades bioativas mencionadas e o perfil químico (qualitativo ou quantitativo) das amostras. Os resultados obtidos evidenciam, sim, que existem concentrações específicas, nas quais estes compostos são mais ativos (e.g., presentes na única amostra obtida no apiário de Aveleda). As amostras de VA demonstraram também propriedades citototóxicas semelhantes para todas as linhas celulares tumorais testadas (MCF -7, NCI -H460, HeLa e HepG2), sendo as linhas MCF -7 (carcinoma de mama) e HeLa (carcinoma cervical) as mais suscetíveis. Apesar disso, as amostras estudadas parecem não ser adequadas para o tratamento de carcinoma de mama, hepatocelular e cervical porque, nas concentrações ativas, as amostras também foram tóxicas para células não tumorais (cultura primária de células de fígado de porco, PLP2). Relativamente ao carcinoma do pulmão, o VA deve ser utilizado abaixo da concentração tóxica para as células não tumorais. Em geral, o presente estudo evidenciou o enorme potencial bioativo do VA, sendo o primeiro trabalho realizado com amostras Portuguesas.Bee venom (BV) or apitoxin is an apiculture product that has been used since ancient times for several applications namely in the traditional medicine apitherapy. It is a complex mixture of substances responsible for different bioactive properties. In the present work, five bee venom samples obtained from Apis mellifera iberiensis from two different apiaries in Bragança (Aveleda and Milhão) were chemically characterized and evaluated for their antioxidant, anti -inflammatory and cytotoxic properties. The LC/DAD/ESI -MSn analysis of the samples showed that melittin was the most abundant compound, followed by phospholipase A2 and apamin. All the samples revealed antioxidant activity, measured by the free radicals scavenging activity, reducing power and lipid peroxidation inhibition, and anti -inflammatory activity, determined by the capacity to inhibit NO formation in murine macrophages (RAW 264,7). However, it was not observed a direct relation between the mentioned bioactive properties and the chemical profile (qualitative or quantitative) of the samples. The results highlight that there are specific concentrations in which these compounds are more active (e.g., in the single sample obtained from Aveleda apiary). The BV samples also showed similar cytotoxicity for all the tested tumor cell lines (MCF -7, NCI -H460, HeLa and HepG2), being MCF -7 (breast carcinoma) and HeLa (cervical carcinoma) the most susceptible ones. Nevertheless, the studied samples seem to be not suitable to treat breast, hepatocellular and cervical carcinoma because at the active concentrations, the samples were also toxic for non -tumor cells (porcine liver primary culture, PLP2). Regarding the non -small lung cell carcinoma, BV should be used under the concentration toxic for non -tumor cells. Overall, the present study corroborates the enormous bioactive potential of BV being the first report on samples from Portugal.À Fundação para a Ciência e Tecnologia (FCT, Portugal) pelo suporte financeiro ao CIMOinfo:eu-repo/semantics/publishedVersio

    Bioactive properties of pollen samples collected in the Northeast of Portugal

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    Reactive oxygen species are formed during normal cellular metabolism, but when present in high concentration they become toxic. Mammalian ce lls possess intracellular defences such as superoxide dismutase, catalase or glutathione peroxidase in order to protect the cells against excessive levels of free radicals

    Insights on the extraction performance of Alkanediols and Glycerol: ssing Juglans regia L. Leaves as a source of bioactive compounds

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    Glycerol and alkanediols are being studied as alternative solvents to extract phytochemicals from plant material, often as hydrogen bond donors in deep eutectic solvents (DESs). Many of those alcohols are liquid at room temperature, yet studies of their use as extraction solvents are scarce. In this work, glycerol and a series of alkanediols (1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, and 1,2-hexanediol) were studied for the extraction of phenolic compounds from Juglans regia L. leaves, a rich source of this class of bioactive compounds. The extraction yield was quantified, and the bioactivity of both extracts and pure solvents was evaluated by measuring the anti-inflammatory and cytotoxic activities. The solvents showing the best combined results were 1,2 and 1,3-propanediol, as their extracts presented a high amount of phenolic compounds, close to the results of ethanol, and similar cytotoxicity against cervical carcinoma cells, with no impact on non-tumor porcine liver cells in the studied concentration range. On the other hand, none of the extracts (and solvents) presented anti-inflammatory activity. Overall, the results obtained in this work contribute to the study of alternative solvents that could potentially be used also as formulation media, highlighting the importance of walnut leaves as a source of bioactive compounds.This work was developed within the scope of the CIMO-Mountain Research Center UIDB/00690/2020 and CICECO-Aveiro Institute of Materials UIDB/50011/2020 & UIDP/50011/2020 projects, both financed by national funds through the Portuguese Foundation for Science and Technology (FCT)/MCTES, as well as POCI-01-0145-FEDER-006984 (LA LSRE-LCM), funded by ERDF, through POCI-COMPETE2020 and FCT. The authors also thank the national funding from FCT, P.I., through the individual scientific employment program-contract for L. Barros and R. C. Calhelha and V. Vieira’s grant (SFRH/BD/108487/2015). Support was also provided by project AllNat—POCI-01-0145-FEDER-030463 (PTDC/EQU-EPQ/30463/2017), funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI), and by national funds through the Foundation for Science and Technology (FCT/MCTES).info:eu-repo/semantics/publishedVersio

    Erythrocyte deformability in a hyperbolic microchannel

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    Serious diseases such as diabetes and malaria are deeply related to microcirculation disorders caused by abnormal erythrocytes deformability [1]. Therefore, various studies on red blood cells (RBCs) deformation have been carried out but those studies rather focus on shear ow or extensional ow [2-6]. In this study, a relatively low aspect ratio (AR) hyperbolic microchannel was used in order to create an extensional ow combined with a shear ow, where AR= h w , h means the depth and w means the width of the microchannel. The objective of the study is to investigate the degree of RBC deformation throughout the microchannel at the centerline (y = 0). The blood samples were RBCs diluted with the Hank's Balanced Salt Solution (HBSS) with the hematocrit (Hct) level set to be 2%. A polydimethylsiloxane (PDMS) microchannel, having a hyperbolic contraction region followed by an abrupt expansion shape, was fabricated by a soft-lithography technique. The dimensions of the microchannel: width of the inlet (w), length of contraction region (l), width of the exit of contraction (wc) and depth (h) were 400 m, 580 m, 20 m and 14 m, respectively. Hence, the AR was 0:035. The experimental equipment consisted of an inverted microscope (Diaphot 300, Nikon), a high-speed camera (FASTCAM SA3, Photron) connected to a computer and a 1mL syringe (TERUMO R SYRING) controlled by a syringe pump (PHD ULTRA). The manufactured PDMS microchannel was placed on the stage of the microscope where the ow rate Q of the working uids was kept constant at 0:5 L=min. The owing RBCs were recorded by a high speed camera at a frame rate of 7500 frames/s and analyzed. The DI was obtained by DI= a b a + b where a refers to the major axis and b refers to the minor axis of the ellipse best tted to RBCs. High DI values in the contraction region were observed. It is possible to say that the RBCs highly elongate with both extensional and shear dominated ows achieved by a hyperbolic microchannel with a relatively low aspect ratio AR

    Assessment of gamma oryzanol variability, an attractive rice bran bioactive compound

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    Gamma-oryzanol is a compound present on rice bran, which has been studied for its bioactive properties, including its cytotoxic activity. The gamma-oryzanol biosynthesis occurs on the lipidic membrane of the plant and can be influenced by edaphoclimatic grown conditions. Two Portuguese rice varieties (Ceres and Macarico) from 6 growing environments were analysed in order to explore the influence of the growing conditions on the gamma-oryzanol content, its constituents, and cytotoxic effect against 4 human tumour cell lines (NCI-H460, HeLa, HepG2, and MCF-7). The overall variability of gamma-oryzanol concentration was from 1.56 g/Kg to 3.19 g/Kg, Ceres reveals higher values than Macarico; those concentrations also varied with the growing environment. The environment was also determinant for the individual concentration of the 3 gamma-oryzanol compounds (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, and campesteryl ferulate). A cytotoxic effect was observed for all the tested tumour cell lines and also varied with the growing environment.This study was financially supported by FEDER (Fundo Europeu de Desenvolvimento Regional, Portugal) under the Program PT2020, Project POCI-01-0247- FEDER-017931 - ArrozBig - Development of rice products with low glycemic index; which also supported C. Pereira research grant. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Program PT2020 for financial support to CIMO ID/AGR/00690/2019 and R. Calhelha contract and to FCT, Portugal for the PhD grant of A. Castanho (SFRH/BD/120929/2016).info:eu-repo/semantics/publishedVersio
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