Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4(1H)-Imine Derivatives

The gas-phase behavior of 12 quinolon-4(1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold. Figure

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Atmospheric Pressure Plasma Pretreatment of Sugarcane Bagasse: the Influence of Biomass Particle Size in the Ozonation Process

Atmospheric pressure O₂ plasma was used to produce ozone in order to treat sugarcane bagasse as a function of particle sizes. The fixed bagasse moisture content was 50 %. The delignification efficiency had small improvement due to ozonation process as a function of particle size, varying from 75 up to 80 %. Few amounts of hemicellulose were removed, but the ozonation has not been affected significantly with particle size variance as well (from 30 up to 35 %). The cellulose presented some losses below 1.0 mm size (8–15 %) which was an unexpected result. The conversion of cellulose content into free sugar has shown a significant increase as the particle size has diminished as well. The best condition of the bagasse particle size was for 0.08 mm. For this case, a great quantity of cellulose (78.8 %) was converted into glucose. Optical absorption spectroscopy was applied to determine ozone concentrations in real time where the samples with typical bagasse particle sizes equal or below to 0.5 mm had shown a better absorption of ozone in comparison with greater particle size samples.     

Terroir Effect on the Phenolic Composition and Chromatic Characteristics of Mencía/Jaen Monovarietal Wines: Bierzo D.O. (Spain) and Dão D.O. (Portugal)

‘Mencía’/‘Jaen’ it’s an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different “terroirs” on the phenolic composition and chromatic characteristics of ‘Mencía’/‘Jaen’ monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from ‘Jaen’ and ‘Mencía’ to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.     

Production of Verbascoside,Isoverbascoside and Phenolic Acids in Callus,Suspension, and Bioreactor Cultures of Verbena officinalis and Biological Properties of Biomass Extracts

Callus, suspension and bioreactor cultures of Verbena officinalis were established, and optimized for biomass growth and production of phenylpropanoid glycosides, phenolic acids, flavonoids and iridoids. All types of cultures were maintained on/in the Murashige and Skoog (MS) media with 1 mg/L BAP and 1 mg/L NAA. The inoculum sizes were optimized in callus and suspension cultures. Moreover, the growth of the culture in two different types of bioreactors—a balloon bioreactor (BB) and a stirred-tank bioreactor (STB) was tested. In methanolic extracts from biomass of all types of in vitro cultures the presence of the same metabolites—verbascoside, isoverbascoside, and six phenolic acids: protocatechuic, chlorogenic, vanillic, caffeic, ferulic and rosmarinic acids was confirmed and quantified by the HPLC-DAD method. In the extracts from lyophilized culture media, no metabolites were found. The main metabolites in biomass extracts were verbascoside and isoverbascoside. Their maximum amounts in g/100 g DW (dry weight) in the tested types of cultures were as follow: 7.25 and 0.61 (callus), 7.06 and 0.48 (suspension), 7.69 and 0.31 (BB), 9.18 and 0.34 (STB). The amounts of phenolic acids were many times lower, max. total content reached of 26.90, 50.72, 19.88, and 36.78 mg/100 g DW, respectively. The highest content of verbascoside and also a high content of isoverbascoside obtained in STB (stirred-tank bioreactor) were 5.3 and 7.8 times higher than in extracts from overground parts of the parent plant. In the extracts from parent plant two iridoids—verbenalin and hastatoside, were also abundant. All investigated biomass extracts and the extracts from parent plant showed the antiproliferative, antioxidant and antibacterial activities. The strongest activities were documented for the cultures maintained in STB. We propose extracts from in vitro cultured biomass of vervain, especially from STB, as a rich source of bioactive metabolites with antiproliferative, antioxidant and antibacterial properties.     

Characterization of the Zwitterionic Intermediate in 1,1‐Carboboration of Alkynes

The reaction of a Lewis acidic borane with an alkyne is a key step in a diverse range of main group transformations. Alkyne 1,1‐carboboration, the Wrackmeyer reaction, is an archetypal transformation of this kind. 1,1‐Carboboration has been proposed to proceed through a zwitterionic intermediate. We report the isolation and spectroscopic, structural and computational characterization of the zwitterionic intermediates generated by reaction of B(C₆F₅)₃ with alkynes. The stepwise reactivity of the zwitterion provides new mechanistic insight for 1,1‐carboboration and wider B(C₆F₅)₃ catalysis. Making use of intramolecular stabilization by a ferrocene substituent, we have characterized the zwitterionic intermediate in the solid state and diverted reactivity towards alkyne cyclotrimerization.     

Doping Polysulfone Membrane with Alpha‐Tocopherol and Alpha‐Lipoic Acid for Suppressing Oxidative Stress Induced by Hemodialysis Treatment

The reduction of free radicals by bioactive membranes used for hemodialysis treatment is an important topic due to the constant rise of oxidative stress‐associated cardiovascular mortality by hemodialysis patients. Therefore, it is urgent to find an effective solution that helps to solve this problem. Polysulfone membranes enriched with α‐lipoic acid, α‐tocopherol, and with both components are fabricated by spin coating. The antioxidant properties of these membranes are evaluated in vitro by determining the lipid‐peroxidation level and the total antioxidant status of the blood plasma. The biocompatibility is assessed by quantifying the protein adsorption, platelet adhesion, complement activation, and hemolytic effect. All types of membranes show in vitro antioxidant activity and a trend to reduce oxidative stress in vivo; the best results show membranes prepared with a combination of both compounds and prove to be nonhemolytic and hemocompatible. Moreover, the membrane specific separation ability for the main waste products is not affected by antioxidants incorporation.     

Evaluation of the cytotoxicity on breast cancer cell of extracts and compounds isolated from Hyptis pectinata (L.) poit

Abstract

Hyptis pectinata is a herb popularly used in Brazil for the treatment of inflammations, pain, bacterial infections and cancer. In the present study, inflorescences (MPIn), leaves (MPL), branches (MPB), root (MPR) extracts and three compounds isolated from MPIn were assayed against breast tumor cell lines. The structures of the three compounds (pectinolide J, hyptolide and pectinolide E) were determined by means of spectroscopic analysis. Pectinolide J was isolated for the first time. The MPIn, MPL and MPR exhibited specific antiproliferative activity on tumor cell lines when compared to normal cell lines with IC₅₀ of 52.01?±?0.64, 45.91?±?0.02?μg/mL and 82.84?±?0.03?μg/mL, respectively. Although the isolated substances did not present good antiproliferative activity, when the three were associated, a greater biological effect was observed, suggesting a synergistic effect. Hyptolide (5.6?±?0.4?μg/mL) showed IC₅₀ sufficiently low to be considered as a drug prototype.     

Development of Phenothiazine Hybrids with Potential Medicinal Interest: A Review

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.     

A comparative study of calibration transfer methods for determination of gasoline quality parameters in three different near infrared spectrometers

This work presents a comparative study of calibration transfer among three near infrared spectrometers for determination of naphthenes and RON (Research Octane Number) in gasoline. Seven transfer methods are compared: direct standardization (DS), piecewise direct standardization (PDS), orthogonal signal correction (OSC), reverse standardization (RS), piecewise reverse standardization (PRS), slope and bias correction (SBC) and model updating (MU). Two pre-treatment procedures, namely standard normal variate (SNV) and multiplicative scatter correction (MSC), are also investigated. The choice of an appropriate number of transfer samples for each technique, as well as the effect of window size in PDS/PRS and OSC components, are discussed. A broad set of gasoline samples representative of the Northeastern states of Brazil is employed in the investigation. The results show that the use of calibration transfer yields prediction errors comparable to those obtained with complete recalibration of the secondary instrument. Overall, the results point to RS as the best method for the analytical problem under consideration. When storage and/or physical transportation of transfer samples are impractical, MU is more appropriate. The comprehensive investigation carried out in the present work will be of value for practitioners involved in networks of fuel monitoring.     

Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.