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.

Antibacterial activity of Ionic Liquids based on ampicillin against resistant bacteria

Antibacterial activity of novel Active Pharmaceutical Ingredient Ionic Liquids (API-ILs) based on ampicillin anion [Amp] have been evaluated. They showed growth inhibition and bactericidal properties on some sensitive bacteria and especially some Gram-negative resistant bacteria when compared to the [Na][Amp] and the initial bromide and chloride salts. For these studies were analysed the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBIC) against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinically isolated), as well as sensitive Gram positive S. Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis and completed using clinically isolated resistent strains: E. coli TEM CTX M9, E. coli CTX M2 and E. coli AmpC Mox. From the obtained MIC values of studied APIs-ILs and standard [Na][Amp] were derived RDIC values (relative decrease of inhibitory concentration). High RDIC values of [C16Pyr][Amp] especially against two resistant Gram-negative strains E. coli TEM CTX M9 (RDIC>1000) and E. coli CTX M2 (RDIC>100) point clearly to a potential promising role of APIs-ILs as antimicrobial drugs especially against resistant bacterial strains.

Analysis of ground reaction force and electromyographic activity of the gastrocnemius muscle during double support

O documento em anexo encontra-se na versão post-print (versão corrigida pelo editor).

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.

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

Angolan cymbopogon citratus used for therapeutic benefits: nutritional composition and influence of solvents in phytochemicals content and antioxidant activity of leaf extracts

Folk medicine is a relevant and effective part of indigenous healthcare systems which are, in practice, totally dependent on traditional healers. An outstanding coincidence between indigenous medicinal plant uses and scientifically proved pharmacological properties of several phytochemicals has been observed along the years. This work focused on the leaves of a medicinal plant traditionally used for therapeutic benefits (Angolan Cymbopogon citratus), in order to evaluate their nutritional value. The bioactive phytochemical composition and antioxidant activity of leaf extracts prepared with different solvents (water, methanol and ethanol) were also evaluated. The plant leaves contained ~60% of carbohydrates, protein (~20%), fat (~5%), ash (~4%) and moisture (~9%). The phytochemicals screening revealed the presence of tannins, flavonoids, and terpenoids in all extracts. Methanolic extracts also contained alkaloids and steroids. Several methods were used to evaluate total antioxidant capacity of the different extracts (DPPH; NO; and H2O2 scavenging assays, reducing power, and FRAP). Ethanolic extracts presented a significantly higher antioxidant activity (p < 0.05) except for FRAP, in which the best results were achieved by the aqueous extracts. Methanolic extracts showed the lowest radical scavenging activities for both DPPH; and NO; radicals.

Effect of peel and seed removal on the nutritional value and antioxidant activity of tomato (Lycopersicon esculentum L.) fruits

The effect of peel and seed removal, two commonly practiced procedures either at home or by the processing industry, on the physicochemical properties, bioactive compounds contents and antioxidant capacity of tomato fruits of four typical Portuguese cultivars (cereja, chucha, rama and redondo) were appraised. Both procedures caused significant nutritional and antioxidant activity losses in fruits of every cultivar. In general, peeling was more detrimental, since it caused a higher decrease in lycopene, bcarotene, ascorbic acid and phenolics contents (averages of 71%, 50%, 14%, and 32%, respectively) and significantly lowered the antioxidant capacity of the fruits (8% and 10%, using DPPH. and b-carotene linoleate model assays, correspondingly). Although seeds removal favored the increase of both color and sweetness, some bioactive compounds (11% of carotenoids and 24% of phenolics) as well as antioxidant capacity (5%) were loss. The studied cultivars were differently influenced by these procedures. The fruits most affected by peeling were those from redondo cultivar (-66% lycopene, -44% b-carotene, -26% ascorbic acid and -38% phenolics). Seeds removal, in turn, was more injurious for cereja tomatoes (-10% lycopene, -38% b-carotene, -25% ascorbic acid and -63% phenolics). Comparatively with the remaining ones, the rama fruits were less affected by the trimming procedures.

Impact of boiling on phytochemicals and antioxidant activity of green vegetables consumed in the Mediterranean diet

The effect of boiling (10 minutes) on eleven green vegetables frequently consumed in the Mediterranean diet was evaluated. For that, some physicochemical parameters and the contents of vitamin C, phenolics and carotenoids, as well as the antioxidant activity, were determined in raw and boiled samples. The raw vegetables analysed in this study were good sources of vitamin C, carotenoids and phenolic compounds, with contents ranging from 10.6 to 255.1 mg/100 g, 0.03 to 3.29 mg/100 g and 202.9 to 1010.7 mg/100 g, respectively. Boiling promoted losses in different extensions considering both the different bioactive compounds and the distinct vegetables analysed. Contrary to phenolics (more resistant), vitamin C was the most affected compound. Boiling also originated significant losses in the antioxidant activity of the vegetables. Considering all the parameters analysed, the vegetables most affected by boiling were broccoli and lettuce. The least affected ones were collard and tronchuda cabbage.

Monomeric and oligomeric flavan-3-ols and antioxidant activity of leaves from different Laurus sp.

The phenolic profile and antioxidant activity of three endemic Laurus sp. from Portugal were analysed. Dried leaves of L. nobilis L., L. azorica (Seub.) Franco, and L. novocanariensis Rivas Mart., Lousã, Fern. Prieto, E. Días, J. C. Costa & C. Aguiar, collected in the mainland and in the Azores and Madeira archipelagos, respectively, were used to prepare different extracts (aqueous, ethanolic and hydroalcoholic). They were studied regarding their DPPH˙ scavenging activity, total phenolic and flavonoid contents, and the main phenolic compounds were identified by HPLC-DAD-ESI-MS/MS. Total flavonoid contents were 30.1, 46.3, and 36.7 mg of epicatechin equivalents per g of sample (dry weight) for L. nobilis, L. azorica and L. novocanariensis, respectively. Epicatechin was the major compound, representing ∼12.1% of total flavan-3-ols in L. nobilis, ∼25.6% in L. azorica, and ∼19.9% in L. novocanariensis. Although all samples presented a similar phenolic profile, significant differences were observed in their total contents and antioxidant activity.

Effects of Chlorophenoxy Herbicides and Their Main Transformation Products on DNA Damage and Acetylcholinesterase Activity

Persistent pesticide transformation products (TPs) are increasingly being detected among different environmental compartments, including groundwater and surface water. However, there is no sufficient experimental data on their toxicological potential to assess the risk associated with TPs, even if their occurrence is known. In this study, the interaction of chlorophenoxy herbicides (MCPA, mecoprop, 2,4-D and dichlorprop) and their main transformation products with calf thymus DNA by UV-visible absorption spectroscopy has been assessed. Additionally, the toxicity of the chlorophenoxy herbicides and TPs was also assessed evaluating the inhibition of acetylcholinesterase activity. On the basis of the results found, it seems that AChE is not the main target of chlorophenoxy herbicides and their TPs. However, the results found showed that the transformation products displayed a higher inhibitory activity when compared with the parent herbicides. The results obtained in the DNA interaction studies showed, in general, a slight effect on the stability of the double helix. However, the data found for 4-chloro-2-methyl-6-nitrophenol suggest that this transformation product can interact with DNA through a noncovalent mode.