221 research outputs found
Novos compostos heterocíclicos de azoto com unidades fenólicas : síntese e actividade biológica
Neste trabalho foi feita a síntese e caracterização de novos compostos que resultaram da combinação de unidades fenólicas com moléculas orgânicas, lineares ou cíclicas, contendo sobretudo átomos de azoto.
A reacção de diaminomaleonitrilo com aldeídos fenólicos permitiu gerar as iminas correspondentes que, na presença de dióxido de manganês ciclizaram para gerar 4,5-diciano-2-hidroxifenil-1H-imidazoles.
Foram preparadas três (Z)-N1-(2-amino-1,2-dicianovinil)-N2-hidroxifenil formamidinas, usadas como reagentes de partida na síntese de 5-amino-4-ciano-1-hidroxifenilimidazoles e 5-amino-4-cianoformimidoil-1-hidroxifenilimidazoles, na presença de base. Esta última família de compostos foi usada na síntese de:
a) 5-amino-4-(1´-amino-2´,2´-dicianovinil)-1-hidroxifenilimidazole, 5,7-diamino-6-ciano-3-hidroxifenil-3H-imidazo[4,5-b]piridina e 5-amino-6,7-diciano-3-hidroxifenil-3H-imidazo[4,5-b]piridina, por reacção com malononitrilo, na ausência ou na presença de base;
b) 6-carbamoil-2,2-dimetil-9-hidroxifenil-1,2-dihidropurina, por reacção com acetona;
c) 6-carbamoil-2,9-dihidroxifenilpurina e 1-carbamoil-6,7-dihidro-3,6-dihidroxifenil-7-imino-imidazo[1,5-e]imidazole, por reacção com aldeídos fenólicos, em diferentes condições experimentais.
Foram sintetizadas várias (Z)-N-[1,2-diciano-2-(hidroxifenilidenamino)vinil]-O-alquilformamidoximas que, na presença de base, sofreram ciclização intramolecular para gerar 6-ciano-8-hidroxifenilpurinas. Por aquecimento com dióxido de manganês, formaram-se 4,5-diciano-N-(N´-alcoxiformimidoil)-2-hidroxifenilimidazoles a partir das mesmas O-alquilformamidoximas.
A reacção de malononitrilo com aldeídos fenólicos permitiu gerar hidroxibenzilidenomalononitrilo, 2-amino-3,5-diciano-6-metoxi-4-hidroxifenilpiridina e o sal de trietilamónio da 2-amino-3,5-diciano-6-dicianometil-4-hidroxifenil-1,4-dihidropiridina, dependendo do solvente utilizado. A reacção de malononitrilo com salicilaldeído originou uma estrutura dimérica desconhecida, que se supõe corresponder a uma unidade de cromeno substituído.
Os compostos sintetizados foram avaliados quanto à sua capacidade antioxidante pela técnica de voltametria cíclica, pelo método de descoloração do radical DPPH e pelo método de degradação da desoxirribose. A actividade antimicrobiana foi igualmente testada, tendo sido avaliado o efeito dos compostos em duas leveduras, Saccharomyces cerevisiae e Candida albicans, e nas bactérias Bacillus subtilis (Gram+) e Escherichia coli (Gram-). Dos 93 compostos sintetizados, 74 dos quais são novos, 21 apresentaram actividade antioxidante, 11 apresentaram actividade antifúngica e 5 apresentaram actividade antibacteriana relevantes.
Os compostos constituídos pelas unidades de imidazole, purina ou seus precursores lineares acoplados com as unidades 3,4-di-hidroxifenilo ou 3,4,5-tri-hidroxifenilo apresentam as actividades antifúngicas mais elevadas, possuindo paralelamente valores de potencial de oxidação baixos e actividades antioxidantes elevadas. Adicionalmente, verificou-se que a ciclização potencia a actividade antifúngica dos compostos e que existe um efeito sinergístico entre a unidade fenólica e a azotada.This work reports the synthesis and characterization of new compounds combining phenolic units with linear or cyclic organic molecules, incorporating mainly nitrogen atoms.
The reaction between diaminomaleonitrile and phenolic aldehydes led to the corresponding imines that, in presence of manganese dioxide cyclized to generate 4,5-dicyano-2-hydroxyphenylimidazoles.
Three different (Z)-N1-(2-amino-1,2-dicyanovinyl)-N2-hydroxyphenyl formamidines were prepared and used as starting materials in the synthesis of the corresponding 5-amino-4-cyano-1-hydroxyphenylimidazoles and 5-amino-4-cyanoformimidoyl-1-hydroxyphenylimidazoles, in the presence of base. This last family of compounds was used in the synthesis of:
a) 5-amino-4-(1´-amino-2´,2´-dicyanovinyl)-1-hydroxyphenylimidazole, 5,7-diamino-6-cyano-3-hydroxyphenyl-3H-imidazo[4,5-b]pyridine and 5-amino-6,7-dicyano-3-hydroxyphenyl-3H-imidazo[4,5-b]pyridine, by reaction with malononitrile, in the absence or in the presence of base;
b) 6-carbamoyl-2,2-dimethyl-9-hydroxyphenyl-1,2-dihydropurine, by reaction with acetone;
c) 6-carbamoyl-2,9-dihydroxyphenylpurine and 1-carbamoyl-6,7-dihydro-3,6-dihydroxyphenyl-7-imino-imidazo[1,5-e]imidazole, by reaction with phenolic aldehydes, under different experimental conditions.
Several (Z)-N-[1,2-dicyano-2-(hydroxylphenylidenamino)vinyl]-O-alkylformamidoximes were synthesized and, in presence of base, cyclized intramolecularly to generate 6-cyano-8-hydroxyphenylpurines. Heating the same O-alkylformamidoximes in the presence manganese dioxide, led to the corresponding 4,5-dicyano-N-(N´-alcoxyformimidoyl)-2-hydroxyphenylimidazoles.
The reaction of malononitrile with phenolic aldehydes generated hydroxybenzylidenemalononitrile, 2-amino-3,5-dicyano-6-methoxy-4-hydroxyphenyl-pyridine and the triethylammonium salt of 2-amino-3,5-dicyano-6-dicyanomethyl-4-hydroxyphenyl-1,4-dihydropyridine, depending on the solvent that was used. The reaction of malononitrile with salicylaldehyde led to an unknown dimeric structure, possibly a substituted chromene.
The compounds were tested for their antioxidant activity by cyclic voltammetry, by the DPPH discoloration method and by the deoxyribose degradation assay. The antimicrobial activity of all compounds was evaluated against two yeasts Saccharomyces cerevisiae and Candida albicans and against bacteria Bacillus subtilis (Gram+) e Escherichia coli (Gram-). From 93 compounds synthetised, 74 are new, 21 presented relevant antioxidant activity, 11 presented antifungal activity and 5 presented antibacterial activity.
The imidazole and purine-based compounds or their linear precursors incorporating 3,4-dihydrophenyl and 3,4,5-trihydroxyphenyl units present the highest antifungal activities, low values for the oxidation potencial and high antioxidant activities. Additionally, the cyclization increased the antifungal activity of the compounds and a synergistic effect between the phenolic and nitrogen units was observed.Fundação para a Ciência e a Tecnologia (FCT) - SFRH / BD / 3185 /2000
Sequential anatectic processes in Mindelo Migmatite Complex (NW Portugal)
O Complexo Migmatítico de Mindelo aflora na orla litoral a norte do Porto sendo composto por um conjunto de litologias diversas incluindo rochas metassedimentares, migmatíticas,graníticas e veios pegmatíticos. As relações de campo, petrografia, geoquímica e assinatura isotópica das diversas litologias permitem deduzir a sequência de processos anatéticos que resultaram na
heterogeneidade litológica presente. A fusão terá ocorrido em diferentes níveis estruturais e consequentemente em condições de pressão e temperatura distintos,resultando em rochas com características específicas: i) a níveis pouco profundos (< 3,5 Kbar)geram-se metatexitos e leucogranitos por migração de leucossomas. Os primeiros melts resultam essencialmente da fusão de quartzo e
plagioclase por fusão húmida seguidos de reacções de fusão incongruente da biotite; (ii) a nível ligeiramente mais profundo a taxa de fusão é superior, o que leva à formação de diatexitos que, sendo menos densos do que a rocha encaixante, intruem os metatexitos; (iii) em níveis ainda mais profundos (~5 Kbar), a composição da rocha,
conjuntamente com temperatura e pressão mais elevadas permitem a fusão da moscovite gerando melts típicos dos granitos de duas micas. Este material ascende na crusta e incorpora abundantes xenólitos formando um corpo granítico muito heterogéneo. Numa fase mais tardia ocorrem processos de metassomatismo potássico com feldspatização, na dependência de circulação de fluidos estruturalmente controlada, em migmatitos e em granitoides. Posteriormente ocorre turmalinização e moscovitização de alguns
granitoides e instalação de veios aplitopegmatíticos.Mindelo Migmatitic Complex outcrops in the coastal-zone,north of Porto. This complex consists on a set of diverse lithologies
including metasedimentary, migmatitic and granitic rocks, and pegmatite veins. Field relationships, petrography, geochemistry and
isotopic signature of these lithologies allow inferring the sequence of anatectic processes that are responsible for the lithological
heterogeneity. The melting occurred at different structural levels, and thus at different pressure and temperature conditions, generating rocks with specific characteristics: i) in shallow levels (<3.5 Kbar)metatexites are produced essentially by water-saturated melting followed by water-undersaturated biotite melting. Leucogranites
resulted from migration of leucosomes; (ii ) in slightly deeper levels the melting rate is higher which leads to the formation of diatexites that intruded metatexites; (iii) in even deeper levels (~ 5 Kbar) higher
pressure and temperature permit the melting of muscovite producing a large amount of typical two-mica granite melts. This material rises in the crust and incorporates abundant xenoliths forming a very heterogeneous granitic body. In subsolidus conditions, structurally controlled metasomatic processes lead to feldspatization of migmatites and granitoids. Later, installation of aplite-pegmatites and local tourmalinization previously formed granitoids took place
Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences
Alcohol. 2010 Mar;44(2):149-56. Epub 2010 Jan 29.
Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences.
Mota A, Guedes F, Areias J, Pinho L, Cardoso MF.
SourceInstituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal.
Abstract
Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males (P<.001) were observed in the group with alcohol intake above 20g/day, as well a lower proportion of patients with HBeAg negativity (P< or =.035). In this group, biochemistry parameters, such as alanine aminotransferase (P=.006), aspartate aminotransferase (P=.001), gamma-glutamyl transferase (P<.001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets (P=.042) and mean corpuscular volume (P<.001) and significantly higher values of prothrombin time (P<.001) in the group with higher levels of alcohol consumption. The characteristics of biopsy (P<.001) and Child-Phug's classification (P=.002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859-468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found concerning association with HBV genotype.
2010 Elsevier Inc. All rights reserved
Complexo Migmatítico de Mindelo (NW de Portugal). Anatexia e relações petrogenéticas
Na orla litoral do norte de Portugal aflora uma faixa referida cartograficamente como “Complexo Granito-Migmatítico” inserida na formação Complexo Xisto-Grauváquico (CXG) [1]. Nesta faixa afloram litologias diversas, nomeadamente: i) rochas metassedimentares; ii) rochas migmatíticas; e, iii) rochas graníticas.
O paleossoma metassedimentar apresenta foliação e bandado composicional marcado por bandas ricas em biotite, estaurolite e almandina e bandas ricas em quartzo e oligóclase(An12-19). As rochas migmatíticas dividem-se em quatro tipos distintos: i) metatexitos mosqueados; ii) metatexitos bandados; iii) diatexitos; e iv) resisters calcossilicatados.
Os metatexitos mosqueados caracterizam-se pela ocorrência de neossoma in situ inserido numa matriz idêntica ao paleossoma. Este define-se por pequenas manchas constituídas por quartzo, plagióclase e cordierite circunscritas por selvedge de biotite. Os metatexitos bandados apresentam alternância entre melanossoma com biotite, silimanite, cordierite e rara almandina e leucossoma quartzofeldspático.
Os diatexitos são rochas de composição essencialmente granítica de grão médio a grosseiro contendo remanescências de material metassedimentar (schlieren) constituídos por alinhamentos de biotite, silimanite, cordierite e rara almandina. O feldspato potássico é geralmente anédrico, substitui a plagioclase, e contém inclusões de todos minerais paragenéticos. A biotite tem bordos arredondados ou simpletíticos em associação com cordierite subédrica.
Os resisters são rochas que pela sua constituição mineralógica não sofreram fusão parcial. Estão inseridos nos migmatitos e são constituídos por metagrauvaques cálcicos com textura granoblástica. Apresentam-se em nódulos elipsoidais, zonados, com espessura e comprimento centimétricos. O zonamento concêntrico destas rochas apresenta um núcleo mais rico em Ca, com diópsido, anortite(An82-92), grossulária(Grs70-90) e quartzo passando a um bordo menos rico em Ca composto por hornblenda, anortite, granada(Grs36-46) e quartzo. Estes núcleos calcossilicatados estão inseridos em camadas tabulares de metagrauvaque com quartzo, plagioclase(An36-44), biotite dispersa e rara almandina. Nas zonas mais ricas em Ca, no núcleo dos nódulos os metagrauvaques permanecem inalterados mas nas zonas exteriores mais pobres em Ca fundem parcialmente resultando um metatexito relativamente rico em Ca e Na.
As rochas graníticas apresentam variação textural desde grão fino a médio. Têm mineralogia típica de granitos de duas micas, por vezes com raros alinhamentos de biotite e silimanite. Contêm xenólitos de metatexito e formam diques discordantes com o encaixante.
Geoquimicamente os metatexitos pelíticos apresentam teores em elementos maiores , traço e padrão de terras raras similares aos xistos estaurolíticos e ao NIBAS [2]. Os nódulos calcossilicatados apresentam enriquecimento em Ca e Mn (Ca>9% e Mn>0,18) no núcleo com empobrecimento gradual para o exterior .
Os granitos são do tipo S, peraluminosos, alcalino-cálcicos, medianamente diferenciados. Os diatexitos são calco-alcalinos e menos diferenciados do que os granitos.
Em todas as litologias, a variação nos teores em “HSFE” (TR, Zr, Hf, Y) está positivamente relacionada com o teor em Fe2O3(t)+MgO. As variações na composição em elementos traço nas litologias referidas serão consequência da variabilidade na incorporação de minerais acessórios a partir do protólito, maioritariamente associados à biotite, condicionada pelas diferenças na composição mineralógica do mesmo e do grau de equilíbrio com o melt..
A assinatura isotópica de todas as litologias é crustal, com εSr330 > 121 e εNd < 0. Relativamente ao εNd330 distinguem-se dois grupos: um grupo que inclui xistos estaurolíticos, migmatitos mosqueados, diatexitos e granitos com valores entre -2,05 e -5,08 e o grupo dos resisters com valores entre -8,12 e -9,30. Os migmatitos bandados apresentam valores que variam entre estes dois grupos distintos. Estes valores permitem considerar uma relação genética entre os granitos, os migmatitos e os xistos estaurolíticos e uma fonte distinta para os metagrauvaques.
Os aspetos litológicos, petrográficos e geoquímicos sugerem três etapas de anatexia/cristalização: i) um primeiro melt resultante da fusão incongruente de biotite, produz minerais anidros (cordierite + plagioclase + quartzo); ii) circulação de fluidos ricos em K por cristalização e diferenciação de melts de níveis mais profundos, onde a taxa de fusão é superior, e que atingindo os migmatitos superiores levam à cristalização de ortoclase e à feldspatização da plagioclase. Esses fluidos, com circulação condicionada estruturalmente, não atingiram todo o complexo migmatítico uma vez que há metatexitos e diatexitos sem feldspato; iii) Nos níveis de maior taxa de fusão há formação de magmas graníticos de tipo S. Estes são menos densos do que as rochas encaixantes o que promove a sua ascensão e instalação, gerando granitos de duas micas, que incorporam xenólitos de migmatitos (metatexíticos e diatexíticos)
From Illness to Resilience: Mediating Factors of Quality of Life in Patients with Congenital Heart Disease
Epidemiological study of genotypes of hepatitis B virus in northerm Portugal
ed Virol. 2009 Jul;81(7):1170-6.
Epidemiological study of genotypes of hepatitis B virus in northern Portugal.
Mota A, Guedes F, Areias J, Pinho L, Cardoso MF.
SourceInstituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Abstract
While the overall prevalence of hepatitis B virus (HBV) infection in Portugal is around 1%, there are no published studies examining HBV genotypes in this country. This study aimed to survey HBV genotypes in the northern Portugal and to examine the possible associations between genotypes and gender, viral transmission routes, viral markers, viral load, and biochemical tests of liver function. The study sample consists of 340 patients with HBV infection of whom 42.9% were women. Tests were carried out for HBV genotypes and biochemical liver function while demographic information, including alcohol intake, was obtained from the patient files. The results indicate the predominance of genotype D (60.3%) and genotype A (31.5%). Intrafamilial transmission was predominant in female patients, while males were infected in equal proportions by perinatal, sexual, and intrafamilial transmission. Absence of HBeAg was found in a significantly smaller proportion of female patients with genotype D as compared to A (56.6% vs. 82.1%, P = 0.028). High viral load was associated significantly and independently with genotype D and HBeAg. Both alanine and aspartate aminotransferases (ALT and AST) were associated with gender and HBeAg. Thus, genotypes A and D were found to be the most prevalent in the north of Portugal. Patients infected with genotype D had higher levels of HBV DNA. HBeAg was associated with genotype D, viral load, and ALT and AST
New synthetic compounds as inhibitors of mycotoxin synthesis
Ochratoxin A (OTA) is a mycotoxin produced by some Aspergillus and Penicillium
species which is often detected in beer, cereals, coffee, feeds, figs, sultanas and
wine. Some fungicides have been found to be effective in preventing fungal
growth, but, in other cases, an increase in the synthesis of mycotoxins was
reported. Also, the pressure to use less harmful compounds to the environment
stimulates the exploration of new and more benign compounds.
Synthetic compounds were tested on the growth and OTA production of one strain
of A. alliaceus, A. ochraceus, A. carbonarius and A. niger. These new synthetic
compounds have a linear structure incorporating urea and/or a phenolic unit.
Fungi were grown in yeast extract sucrose (YES) medium supplemented with 50
μM to 200 μM of each one of 20 test compounds in triplicate, for 6 days. Growth
was recorded by measuring the diameter of colonies every 24 hours, and OTA was
quantified after 5 days of growth using HPLC and fluorescence detection.
Growth of the A. ochraceus and the A. carbonarius strains were not inhibited by
most of these compounds. However, some led to a decrease in OTA detection.
Compounds without the phenolic unit were found to be less effective, while those
compounds with urea and phenolic units were the most effective. Growth of the A.
alliaceus and of the A. niger strains were inhibited by compound-X by 22 and 27%
respectively.
This approach will lead to the selection of functional groups able to inhibit the
synthesis of OTA which could be incorporated into more powerful antifungal
compounds.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/11228/2002, SFRH/BD/3185/2000, SFRH/BPD/12044/2003
Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential
In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds. The results obtained with cellular models (L929 and PC12) show that they are not toxic and really protect from membrane lipid peroxidation induced by the ascorbate-iron oxidant pair. The level of protection correlates with the drugs lipophilic profile and is sometimes superior to trolox and equivalent to that observed for a-tocopherol. The compounds FMA4 and FMA7 presented also a high protection from cell death evaluated in the presence of a staurosporine apoptotic stimulus. That protection results in a significant reduction of caspase-3 activity induced by staurosporine which by its turn seems to result from a protection observed in the membrane receptor pathway (caspase-8) together with a protection observed in the mitochondrial pathway (caspase-9). Taken together the results obtained with the new compounds, with linear chains, open up perspectives for their use as therapeutical agents, namely as antioxidants and protectors of apoptotic pathways. On the other hand the slight pro-oxidant profile obtained with the cyclic structures suggests a different therapeutic potential that is under current investigation.Fundação para a Ciência e a Tecnologia (FCT) - POCTI and/or FEDER programmes,
SFRH/BD/17174/2004, SFRH/BD/3185/2000
Cell adhesion and proliferation of skeletal muscle cells on piezoelectric poly(vinylidene fluoride) membranes
Several body tissues, including bone and muscle, are subjected to electromechanical solicitations during their functional activity [1-3]. Thus, the use of electroactive polymers as active scaffolds shows innovative large potential for tissue engineering applications as it offers functional resemblance to biological clues [2]. In particular, piezoelectric polymers have shown suitability for tissue engineering due to their ability to vary surface charge when a mechanical load is applied [4] and their possibility to be processed in form of films, porous 2D and 3D membranes and scaffolds and fiber mats.
The influence of poling state and morphology (film or fiber morphology) of
piezoelectric poly(vinylidene fluoride) (PVDF) on the adhesion and morphology of
myoblast cells was studied. Non-poled, ‘‘poled +’’ and “poled-’’ !-PVDF films were prepared by solvent casting followed by corona poling. Further, random and aligned electrospun !-PVDF fiber mats were also prepared. It is demonstrated that negatively charged surfaces improve cell adhesion and proliferation and that the directional growth of the myoblast cells can be achieved by culturing the cell on aligned fibers.
Therefore, the potential application of electroative materials for muscle regeneration is demonstrated
Biomechanical Study of the Vestibular System of the Inner Ear Using a Numerical Method
The inner ear has two main parts, the cochlea, dedicated to hearing, and the vestibular system, dedicated to balance. Dizziness and vertigo are the main symptoms related to vestibular disorders, which commonly affects older people. In order to eliminate these symptoms a vestibular rehabilitation is performed; this consists in a range of movements of the head, known as maneuvers, performed by a clinical professional. This procedure does not always work as expected. The aim of this work is to contribute to a better understanding on how the vestibular system works. This knowledge will help in the development of new techniques that will facilitate a more efficient rehabilitation. In order to achieve that goal, a three-dimensional numerical model of the vestibular system, containing the fluids which promote the body balance, was constructed. The vestibular components will be discretized using the finite element method and the fluid flow will be analyzed using the Smoothed Particle Hydrodynamics
The results obtained with the numerical model of the semicircular canal built to study the rehabilitation process are presented and compared with other authors. The solution achieved is similar with literature.info:eu-repo/semantics/publishedVersio
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