Antimicrobial activity of quinoxaline 1,4-dioxide and three derivatives

O presente trabalho descreve o estudo da actividad e antimicrobiana de quarto derivados da quinoxalina N,N-dióxido: quinoxalina 1,4-dióxido, 2-metilquinoxalina 1,4- dióxido, 6-cloro-2,3-dimetilquinoxalina 1,4-dióxido e 3-benzoil-2-metilquinoxalina 1,4- dióxido contra as estirpes bacterianas Geobacillus stearothermophilus ATCC 10149, Escherichia coli ATCC 25922, Escherichia coli HB101, Escherichia coli (blaTEM, blaCTX-M) e Salmonella (blaCTX-M), assim como contra a estirpe de levedura Saccharomyces cerevisiae PYCC 4072. A determinação da concentração mínima inibitória (MIC) foi realizada pelo método de diluição. Os valores de MIC’s foram estimados para cada composto e estirpe. Os resultados obtidos sugerem potenciais novas drogas para quimioterapia.

Antimicrobial activity of pyrazine and quinoxaline N,N’-dioxide heterocyclic compounds

The nitrogen heterocyclic organic compounds 1,4 dioxide pyrazine and quinoxaline derivatives have been widely studied due to their potential use as synthetic drugs. The thermochemical study of three N,N´-dioxides: 2,3,5-trimethylpyrazine-1,4-dioxide, tetramethylpyrazine-1,4-dioxide and 6-chloro-2,3-dimethilquinoxaline 1,4-dioxide has been recently developed in order to establish relationships among the energetical, structural and reactivity properties [4,5]. Several studies have reported their pharmacological activity, particularly as antimicrobial agents [1,2,3]. It has also been established a relation between energetical and structural properties and biological activity, once these compounds present N – oxide bonds, increasing their oxidative capacity. The present work reports the study of antimicrobial activity for those compounds against the bacteria Geobacillus stearothermophylus, Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and also against the yeasts Saccharomyces cerevisiae PYCC 4072, Candida albicans PYCC3436T, Candida tropicalis PYCC, Issatchenka Orientalis PYCC. The determination of the minimal inhibitory concentration (MIC), points to an antimicrobial activity and the preliminary results indicate that these compounds may be potential candidates as antimicrobial drugs with clinical, agriculture or food industries applications.

Antifungal activity of Imidazolidin-4-ones of the antimalarial primaquine

The 5-Isopropyl-3-[4-(6-methoxy-quinolin-8-ylamino)-pentyl]-2,2-dimethyl-imidazolidin-4-one (ValPQacet) was sinthesized through acylation of the anti-malarial primaquine with α-valine and subsequent reaction of the resulting -aminoamide with propanone (Sheme 1).Imidazolidin-4-ones of the anti malarial primaquine are being sinthesized to develop new variants in order to improve more effective treatments against malaria . Recently it has been observed that primaquine derivates could have effect in a new kind of yeast . To study the fungicidal activity against Candida albicans, Candida tropicalis, Issatchenkia orientalis, Sacharomyces cerevisae, the ValPQacet was put in the form of the hydrochloride salt. The minimal inhibitory concentration (MIC) could be determined for all yeast in the concentration range assayed. Also was determined MIC’s of primaquine hydrochloride salt for all yeast, and this shows that the parent drug is less active than our compound. Further studies are being performed to determine viability and cellular injury with this drugs.

Synthesis, characterization and antiproliferative activity on cancer cell lines of new ionic liquids from ampicillin

Ionic Liquids (ILs) are ionic compounds that possess melting temperature below 100ºC and they have been a topic of great interest since the mid-1990s due to their unique properties. The range of IL uses has been broadened, due to a significant increase in the variety of physical, chemical and biological ILs properties. They are now used as Active Pharmaceutical Ingredients (APIs) and recent interests are focused on their application as innovative solutions in new medical treatment and delivery options.1 In this work, our principal objective was the synthesis and investigation of physicochemical and medical properties of ionic liquids (ILs) and organic salts from ampicillin. This approach is of huge interest in pharmaceutical industry as cation and anion composition of ILs and organic salts can greatly alter their desired properties, namely the melting temperature and even synergistic effects can be obtained.2,3 For the synthesis of these compounds we used a recently developed method proposed by Ohno et al.4 for the preparation of quaternary ammonium and phosphonium hydroxides, that were neutralized by ampicillin. After purification we obtained pure ILs and salts in good yields. These ILs shows good antimicrobial and antifungal activities. As it is well known that some ionic liquids containing phosphonium and ammonium cation also shows anti-cancer activity1,5 we also decided to study these compounds against some cancer cell lines.

Fungidal and bacterial activity of N,N-dimethyl-4-(2,2,2-trichloro-1-(phenylamino)ethyl)aniline

N,N-dimethyl-4-((phenylamino)methyl)aniline (1) was prepared by condensation of aniline and 4-(dimethylamino)benzaldehyde [1] N,N-dimethyl-4-(2,2,2-trichloro-1-(phenylamino)ethyl)aniline (2) was synthesized by trichloromethylation of the imine (N,N-dimethyl-4-((phenylimino)methyl)aniline (1)) with trichloroacetic anhydride under microwave irradiation [2] (Sheme 1). The present work reports the study of bacterial and yeast activity for the compound 2. The bacteria used in this study are Staphylococcus aureus, Escherichia coli and the yeast are Saccharomyces Cerevisiae Candida albican.The results that we will present are the determination of minimal inhibitory concentration (MIC), by means of microdilution by plate method and the specific growth constants for this microorganism. Further studies are being performed to determine viability and cellular injury with this drug.

Strawberries from integrated pest management and organic farming: phenolic composition and antioxidant properties

Consumer awareness, pesticide and fertilizer contaminations and environmental concerns have resulted in significant demand for organically grown farm produce. Consumption of berries has become popular among health-conscious consumers due to the high levels of valuable antioxidants, such as anthocyanins and other phenolic compounds. The present study evaluated the influence that organic farming (OF) and integrated pest management (IPM) practise exert on the total phenolic content in 22 strawberry samples from four varieties. Postharvest performance of OF and IPM strawberries grown in the same area in the centre of Portugal and harvested at the same maturity stage were compared. Chemical profiles (phenolic compounds) were determined with the aid of HPLC-DAD/MS. Total phenolic content was higher for OF strawberry extracts. This study showed that the main differences in bioactive phytochemicals between organically and IPM grown strawberries concerned their anthocyanin levels. Organically grown strawberries were significantly higher in antioxidant activity than were the IPM strawberries, as measured by DPPH and FRAP assays.

Teas, dietary supplements and fruit juices: a comparative study regarding antioxidant activity and bioactive compounds

Nowadays, new emerging products claiming antioxidant properties are becoming more frequent. However, information about this topic in their labels is usually scarce. In this paper, we analyzed total phenolics, total flavonoids and ascorbic acid contents, as well as DPPH scavenging activity of several commercial samples, namely green tea and other herbal infusions, dietary supplements, and fruit juices, available in the Portuguese market. In general, beverages containing green tea and hibiscus showed higher phenolics contents (including flavonoids) and antioxidant activity than those without these ingredients. A borututu infusion presented the lowest concentrations of bioactive compounds and scavenging activity, due to the low recommended amount of plant to prepare the beverage. Some juices without antioxidant claims in the label presented similar values to those with it.

Evaluation of 99mTc-Sestamibi as a potential tool to investigate PgP activity in inflammation

Introduction: In the XXI Century ’s Society the scientific investigation process has been growing steadily , and the field of the pharmaceutical research is one of the most enthusiastic and relevant . Here, it is very important to correlate observed functional alterations with possibly modified drug bio distribution patterns . Cancer, inflammation and inf ection are processes that induce many molecular intermediates like cytokines, chemokines and other chemical complexes that can alter the pharmacokinetics of many drugs. One cause of such changes is thought to be the modulator action of these complexes in t he P - Glyco p rotein activity, because they can act like inducers/inhibitors of MDR - 1 expression. This protein results from the expression of MDR - 1 gene, and acts as an ATP energy - dependent efflux pump, with their substrates including many drugs , like antiretrovirals, anticancers, anti - infectives, immunosuppressants, steroids or opioids . Objectives: Because of the lack of methods to provide helpful information in the investigation of in vivo molecular changes in Pgp activity during infection/infl ammation processes, and its value in the explanation of the altered drug pharmacokinetic, this paper want to evaluate the potential utility of 99m Tc - Sestamibi scintigraphy during this kind of health sciences investigation. Although the a im is indeed to create a technique to the in vivo study of Pgp activity, this preliminary Project only reaches the in vitro study phase, assumed as the first step in a n evaluation period for a new tool development. Materials and Methods: For that reason , we are performing in vitro studies of influx and efflux of 99m Tc - Sestamibi ( that is a substrate of Pgp) in hepatocytes cell line (HepG2). We are interested in clarify the cellular behavior of this radiopharmaceutical in Lipopolysaccharide(LPS) stimulated cells ( well known in vitro model of inflammation) to possibly approve this methodology. To validate the results, the Pgp expression will be finally evaluated using Western Blot technique. Results: Up to this moment , we still don’t have the final results, but we have already enough data to let us believe that LPS stimulation induce a downregulation of MDR - 1, and consequently Pgp, which could conduce to a prolonged retention of 99m Tc - Sestamibi in the inflamed cells . Conclusions: If and when this methodology demonstrate the promising results we expect, one will be able to con clude that Nuclear Medicine is an important tool to help evidence based research also on this specific field .

Valorização de subprodutos da vinha e do vinho: impacto do tempo e métodos de preservação nas suas características

Os polifenóis constituem um grupo biologicamente relevante de compostos naturais, que têm gerado um crescente interesse por parte dos consumidores e das indústrias alimentar, farmacêutica e de cosméticos. Os compostos fenólicos exibem uma vasta gama de propriedades fisiológicas, tais como anti-alérgica, anti-aterogénica, anti-inflamatória, anti-microbiana, antioxidante, anti-trombótica, possuindo efeitos cardio-protetores e vasodilatadores. Por conseguinte, o interesse na obtenção deste compostos ativos de uma forma fácil, barata e rápida tem vindo a aumentar. Uma das fontes de polifenóis são os subprodutos agrícolas, tais como os produtos derivados do vinho e/ou processamento de uvas. As folhas, os caules e os resíduos obtidos durante o processo de produção do vinho têm sido subutilizados, apesar de representarem uma boa fonte de compostos antioxidantes e bioativos. Portugal é um dos mais importantes países produtores de vinho, onde todos os anos são geradas várias toneladas de subprodutos associados a esta indústria. A extração, caracterização, quantificação e avaliação da atividade antioxidante de compostos bioativos extraídos destes subprodutos são, pois, tarefas importantes a fim de avaliar o potencial de utilização destes produtos como novas fontes de compostos antioxidantes. O objetivo deste trabalho foi quantificar e avaliar os teores de polifenóis de extratos preparados a partir de folhas e caules de videira, e bagaço, engaço e grainha de uva. Os parâmetros experimentais da extração foram otimizados, incluindo a proporção de solvente de extração (água/etanol), a temperatura e o tempo de extração. A quantificação dos polifenóis (como fenóis totais e flavonoides) foi efetuada por espetrofotometria de UV/Vis. Verificou-se que a melhor razão de solventes extratores foi de 50/50 (v/v) em água/etanol para todos os subprodutos estudados. No caso dos subprodutos folhas e caules, as condições ideais de extração foram obtidas quando se usou uma temperatura de 40ºC e um tempo de extração de 30 min. Para o bagaço, a temperatura ideal foi de 55ºC durante 5 min. Para o engaço e grainha a utilização de uma temperatura de 40ºC durante 5 min e 30 min, respetivamente, revelou-se o ideal para se obter os compostos. Com este trabalho conclui-se que os subprodutos da vinha e do vinho efetivamente possuem compostos de elevado valor e com capacidade antioxidante.

Avaliação da influência de antioxidantes na estabilização de biodiesel

O biodiesel é uma fonte de energia renovável, que se pode obter pela transformação dos resíduos domésticos, e é ambientalmente inócuo, e fácil de transportar, pois tem um ponto de fulgor elevado. Atualmente tem-se focado a atenção nos efeitos da oxidação do biodiesel causados pelo contato com o ar ambiente durante o seu armazenamento. Os produtores, fornecedores e consumidores, pretendem garantir que a qualidade do biodiesel e das suas misturas com combustíveis destilados do petróleo, mantém-se durante longos períodos de armazenamento. A maioria dos óleos vegetais e das gorduras animais, usados como matéria – prima, são triacilgliceróis com grupos ácido gordos de cadeia longa (C16 – C18) ligados por ligações éster a uma estrutura de glicerol. O objetivo deste estudo foi avaliar a eficiência do ácido gálhico e seus derivados alquilo ésteres aumentando a resistência relativa à oxidação do ácido linoléico, inibindo a peroxidação ácido gordos de cadeia longa insaturados. Outro objetivo foi estudar a taxa de inibição da auto-oxidação do ácido linoleico. Foi, ainda estudado o efeito que a concentração do antioxidante, tinha na estabilidade do ácido linoleico. No caso do ácido gálhico verificou-se que o aumento para o dobro da concentração do antioxidante utilizada, obtinha-se quase o dobro da taxa de inibição da oxidação do ácido linoleico. A auto-oxidação de ácido linoleico é acompanhada pela formação do seu dieno conjugado, o qual foi medido sua absorvância, durante 7 dias, por espetrofotometria de absorção UV a 234 nm. Uma diminuição da taxa de formação de dieno conjugado, indica o aumento da atividade antioxidante do composto adicionado à micela de ácido linoleico. Os resultados obtidos permitem concluir que de todos os antioxidantes testados o galhato de butilo é o que possibilita uma maior inibição da oxidação do ácido linoleico para as duas concentrações de antioxidantes testadas (0,1 mM e 1mM), obteve-se uma percentagem de inibição do ácido linoleico de 54,0% e 63,6%, respetivamente. O estudo comparativo da estabilização do ácido linoleico com o antioxidante de referência, o butil -hidroxitolueno, mostrou que este composto tem um poder de estabilização inferior a qualquer dos antioxidantes estudados. Os resultados deste estudo demonstraram que a utilização de compostos fenólicos, em especial o galhato de butilo, constitui uma boa alternativa para a estabilização de matrizes lipídicas, nomeadamente de combustíveis como o biodiesel.

Síntese de derivados de ácidos fenólicos e estudo da sua actividade antioxidante

A peroxidação lipídica, além de causar sérios danos no corpo humano, é a principal causa da deterioração dos alimentos afectando a sua cor, aroma e valor nutricional, o que conduz a uma diminuição do seu ciclo de vida. O fenómeno de oxidação pode ser retardado com recurso a antioxidantes, de origem natural ou sintética, que inibam a formação de espécies reactivas, ou que reajam com estas, formando posteriormente radicais com menor grau de reactividade. Nesta dissertação procedeu-se à síntese e elucidação estrutural de novos antioxidantes, derivados dos ácidos 3,4-diidroxibenzóico (PCA) e 3,4-diidroxifenilacético (DOPAC), e à avaliação da sua actividade anti-radicalar e antioxidante. Os novos antioxidantes sintetizados foram caracterizados usando RMN de 1H e de 13C, FTIR e EM-IE. A avaliação da actividade antioxidante foi realizada com base no método do radical 2,2- difenil-1-picrilhidrazilo (DPPH·) e por técnicas electroquímicas (voltametria de impulso diferencial e voltametria cíclica). Os resultados obtidos permitiram concluir que a eficácia anti-radicalar (AE) é determinada por aspectos da estrutura molecular dos compostos, nomeadamente pela presença de grupos hidroxilo no anel aromático e também de grupos extensores relativamente à posição do grupo carboxílico. Os resultados permitiram verificar que o DOPAC apresenta a mais elevada eficiência anti-radicalar dos compostos em estudo, incluindo o trolox e o ácido gálhico (compostos de referência). Com base nos resultados obtidos concluiu-se que, um menor potencial de oxidação conduz a uma melhor actividade anti-radicalar dos compostos. De facto, verificou-se para o PCA e respectivos ésteres o maior potencial de oxidação e também a menor eficiência anti-radicalar. Em contrapartida, os antioxidantes com maior eficiência anti-radicalar, DOPAC, trolox e ácido gálhico, apresentaram menor potencial de oxidação.

Antitumor activity of hierridin B, a cyanobacterial secondary metabolite found in both filamentous and unicellular marine strains

Cyanobacteria are widely recognized as a valuable source of bioactive metabolites. The majority of such compounds have been isolated from so-called complex cyanobacteria, such as filamentous or colonial forms, which usually display a larger number of biosynthetic gene clusters in their genomes, when compared to free-living unicellular forms. Nevertheless, picocyanobacteria are also known to have potential to produce bioactive natural products. Here, we report the isolation of hierridin B from the marine picocyanobacterium Cyanobium sp. LEGE 06113. This compound had previously been isolated from the filamentous epiphytic cyanobacterium Phormidium ectocarpi SAG 60.90, and had been shown to possess antiplasmodial activity. A phylogenetic analysis of the 16S rRNA gene from both strains confirmed that these cyanobacteria derive from different evolutionary lineages. We further investigated the biological activity of hierridin B, and tested its cytotoxicity towards a panel of human cancer cell lines; it showed selective cytotoxicity towards HT-29 colon adenocarcinoma cells.

Food consumption, physical activity and socio-economic status related to BMI, waist circumference and waist-to-height ratio in adolescents

Objective: To examine the association between obesity and food group intakes, physical activity and socio-economic status in adolescents. Design: A cross-sectional study was carried out in 2008. Cole’s cut-off points were used to categorize BMI. Abdominal obesity was defined by a waist circumference at or above the 90th percentile, as well as a waist-to-height ratio at or above 0?500. Diet was evaluated using an FFQ, and the food group consumption was categorized using sex-specific tertiles of each food group amount. Physical activity was assessed via a self-report questionnaire. Socio-economic status was assessed referring to parental education and employment status. Data were analysed separately for girls and boys and the associations among food consumption, physical activity, socio-economic status and BMI, waist circumference and waist-to-height ratio were evaluated using logistic regression analysis, adjusting the results for potential confounders. Setting: Public schools in the Azorean Archipelago, Portugal. Subjects: Adolescents (n 1209) aged 15–18 years. Results: After adjustment, in boys, higher intake of ready-to-eat cereals was a negative predictor while vegetables were a positive predictor of overweight/ obesity and abdominal obesity. Active boys had lower odds of abdominal obesity compared with inactive boys. Boys whose mother showed a low education level had higher odds of abdominal obesity compared with boys whose mother presented a high education level. Concerning girls, higher intake of sweets and pastries was a negative predictor of overweight/obesity and abdominal obesity. Girls in tertile 2 of milk intake had lower odds of abdominal obesity than those in tertile 1. Girls whose father had no relationship with employment displayed higher odds of abdominal obesity compared with girls whose father had high employment status. Conclusions: We have found that different measures of obesity have distinct associations with food group intakes, physical activity and socio-economic status.

Relationship of milk intake and physical activity to abdominal obesity among adolescents

Background: Diet and physical activity (PA) are recognized as important factors to prevent abdominal obesity (AO), which is strongly associated with chronic diseases. Some studies have reported an inverse association between milk consumption and AO. Objective: This study examined the association between milk intake, PA and AO in adolescents. Methods: A cross-sectional study was conducted with 1209 adolescents, aged 15–18 from the Azorean Archipelago, Portugal in 2008. AO was defined by a waist circumference at or above the 90th percentile. Adolescent food intake was measured using a semi-quantitative food frequency questionnaire, and milk intake was categorized as ‘low milk intake’ (<2 servings per day) or ‘high milk intake’ ( 2 servings per day). PA was assessed via a self-report questionnaire, and participants were divided into active (>10 points) and low-active groups ( 10 points) on the basis of their reported PA. They were then divided into four smaller groups, according to milk intake and PA: (i) low milk intake/low active; (ii) low milk intake/active; (iii) high milk intake/low active and (iv) high milk intake/active. The association between milk intake, PA and AO was evaluated using logistic regression analysis, and the results were adjusted for demographic, body mass index, pubertal stage and dietary confounders. Results: In this study, the majority of adolescents consumed semi-skimmed or skimmed milk (92.3%). The group of adolescents with high level of milk intake and active had a lower proportion of AO than did other groups (low milk intake/low active: 34.2%; low milk intake/active: 26.9%; high milk intake/low active: 25.7%; high milk intake/active: 21.9%, P = 0.008). After adjusting for confounders, low-active and active adolescents with high levels of milk intake were less likely to have AO, compared with low-active adolescents with low milk intake (high milk intake/low active, odds ratio [OR] = 0.412, 95% confidence intervals [CI]: 0.201– 0.845; high milk intake/active adolescents, OR = 0.445, 95% CI: 0.235–0.845).Conclusion: High milk intake seems to have a protective effect on AO, regardless of PA level