Study of antiviral and virucidal activities of aqueous extract of Baccharis articulata against Herpes suis virus

Baccharis articulata is native of América and traditionally used for the treatment of digestive disorders and urinary infections. Cytotoxicity of aqueous extracts of B. articulata was investigated in Vero cells. As the maximal non cytotoxic concentration has been established, this concentration has been used to evaluate antiviral and virucidal activities against Herpes suis virus type 1, member of the same subfamily of Herpes simplex virus. Aqueous extracts of B. articulata exhibited more than 95% of virucidal activity. These findings support their potential application as a disinfectant or antiseptic with low toxicity and provide a valuable knowledge to ethnopharmacology properties of Baccharis articulata.     

A 'Sleeping Trojan Horse' which transports metal ions into cells, localises in nucleoli, and has potential for bimodal fluorescence/PET imaging

A rhenium polypyridine-based molecular vessel is membrane impermeant when empty, but, upon loading with metal ions, the cationic form is taken up by MCF-7 cells, localising in nucleoli. The luminescence of the vessel and its copper binding ability suggest potential as a bimodal fluorescence/PET imaging agent.     

Chiral Determination of Salbutamol,Salmeterol and Atenolol by Two-Dimensional LC–LC: Application to Urine Samples

A heart-cut two-dimensional high-performance liquid chromatography method for enantiomeric determination of salbutamol, salmeterol and atenolol in urine is presented. It involves the use of two separations in a liquid chromatography–liquid chromatography achiral–chiral coupling. Target compounds were previously separated in a primary column (Kinetex™ HILIC, 2.6 μm, 150 × 2.1 mm I.D.) with a mixture of MeOH:ACN:ammonium acetate buffer (5 mM, pH 6) 90:5:5 (v/v/v) as mobile phase at a flow rate of 0.40 mL min⁻¹. Enantiomeric separation was carried out by transferring peak of each compound through a switching valve to a vancomycin chiral column (Chirobiotic™ V, 2.6 μm, 150 × 2.1 mm I.D.) using MeOH:ammonium acetate buffer (2 mM, pH 4) 97:3 (v/v) as mobile phase at a flow rate of 0.50 mL min⁻¹. Ultraviolet detection was done at 227 nm. The method was applied to determine target analytes in urine samples after enzymatic hydrolysis with β-glucuronidase from Helix pomatia, followed by a solid-phase extraction procedure using Isolute^® HCX mixed-mode cartridges. Extraction recoveries ranged from 82 to 90 % in urine samples. Detection limits were 0.091–0.095 μg for each enantiomer of atenolol and between 0.058 and 0.076 and 0.18–0.14 μg for enantiomers of salbutamol and salmeterol, respectively (3 mL of urine). Linearity ranges were between 0.5 and 10 μg mL⁻¹. Intraday and interday reproducibilities of enantiomeric ratio and enantiomeric fraction, expressed as relative standard deviation, were between 1.9 and 9.0 %. The optimized method was successfully applied to the analysis of urine samples obtained from excretion studies in volunteers and in freeze-dried urine samples, containing urinary components with MW < 10,000 and components with MW > 10,000, spiked with different amounts of studied drugs.

     

Terpyridine-fused polyaromatic hydrocarbons generated via cyclodehydrogenation and used as ligands in Ru(II) complexes

A series of novel fused 4'-substituted 2,2'?:?6',2'-terpyridine ligands and their ruthenium(II) complexes were prepared. The unusual 4'-substituents comprised 2,3,4,5-pentaphenylbenzene and its tert-butyl derivative (1 and 2) and the products from oxidative cyclodehydrogenation, i.e. polyaromatic fragments consisting of ten or thirteen fused benzene rings (3 and 4). The syntheses of all the ligands are discussed in terms of the demands and limitations of the Scholl reaction. The optical properties of the ligands, along with the single-crystal X-ray structures of 1 and 2, are presented. The latter show that the pentaphenylbenzene and terpyridine appendages of 1 and 2 are perpendicular in the solid state. Despite the inclusion of the large organic chromophore the absorption and emission properties of the Ru(II) bis-terpy complexes (of ligands 1, 2 and 3) were found to be comparable to those of [Ru(terpy)(2)](2+). They are non-emissive at room temperature but emit at 77 K with excited state lifetimes of 11-12 μs.     

Modeling the binding of peptides on carbon nanotubes and their use as protein and DNA carriers

An in-depth study of a novel functionalization of carbon nanotubes for their application as protein and DNA carriers is presented. First, the optimum conditions for the dispersion of single-walled carbon nanotubes (SWCNTs) with amphiphilic polypeptides were obtained, and the SWCNT–polypeptide complexes were characterized by different techniques (UV–Vis-NIR, CD, and AFM). Based on the properties of the SWCNT–polypeptide complexes, a model that characterizes the adsorption of natural proteins onto SWCNT was described for the first time. This model predicts the adsorption of natural proteins on SWCNTs based on the protein structure and composition, and therefore, allows the design of methods for the preparation of SWCNT–protein complexes. Besides, the use of cationic-designed amphiphilic polypeptides to disperse SWCNTs is applied for subsequent and efficient binding of DNA to carbon nanotubes by a bilayer approach. Therefore, in this article, we develop procedures for the use of SWCNTs as protein and DNA carriers. The systems were delivered into cells showing that the efficiency of delivery is affected by the charge of the complexes, which has important implications in the use of SWCNT as platforms for protein and DNA binding and subsequent use as delivery systems.     

One‐Pot Synthesis of Pentasubstituted Cyclohexanes by a Michael Addition Followed by a Tandem Inter–Intra Double Henry Reaction

Michael, Henry, and Henry : A new one‐pot reaction of α,β‐unsaturated aldehydes and β‐dicarbonyls, which involves a Michael reaction catalyzed by diarylprolinol ethers and an inter–intramolecular Henry tandem reaction catalyzed by TBAF (see scheme), has been developed. The reaction proceeds in high enantio‐ and diastereoselectivity for a wide range of unsaturated aldehydes and β‐dicarbonyl reagents.

     

Zinc and Copper Ions Induce Aggregation of Human β-Crystallins

Cataracts are defined as the clouding of the lens due to the formation of insoluble protein aggregates. Metal ions exposure has been recognized as a risk factor in the cataract formation process. The γ and β crystallins are members of a larger family and share several structural features. Several studies have shown that copper and zinc ions induce the formation of γ-crystallins aggregates. However, the interaction of metal ions with β-crystallins, some of the most abundant crystallins in the lens, has not been explored until now. Here, we evaluate the effect of Cu(II) and Zn(II) ions on the aggregation of HβA1, as a representative of the acidic form, and HβB2, as a representative of the basic β-crystallins. We used several biophysical techniques and computational methods to show that Cu(II) and Zn(II) induce aggregation following different pathways. Both metal ions destabilize the proteins and impact protein folding. Copper induced a small conformational change in HβA1, leading to high-molecular-weight light-scattering aggregates, while zinc is more aggressive towards HβB2 and induces a larger conformational change. Our work provides information on the mechanisms of metal-induced aggregation of β-crystallins.     

Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer—Strategy to Improve Its Efficiency When Administered Orally

Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.     

Multi-class determination of antimicrobials in meat by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry

A multi-residue method using pressurized liquid extraction (PLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for determining trace levels of 31 antimicrobials, including beta-lactams, lincosamides, macrolides, quinolones, sulfonamides, tetracyclines, nitroimidazoles and trimethoprim. The extraction method required pre-homogeneization of the meat with EDTA-washed sand and subsequent one-static-cycle extraction for 10 min with 40 ml of water at 1500 psi and 70 degrees C. The effect of operation temperature, pressure, flush volume, and static cycles on PLE performance was studied. Average recoveries ranged from 75 to 99% with relative standard deviations <18%. The method was validated according to the European Union requirements (2002/657/EC). In addition to the quality parameters included in that decision, the limits of detection (LODs) and quantification (LOQs) were determined. The use of LC-MS/MS provided LODs (between 3 and 15 microg kg(-1)) and LOQs (between 10 and 50 microg kg(-1)), by far lower than half of their maximum residue limits (MRLs) (between 50 and 1200 microg kg(-1)). Confirmation of the presence of any of the studied compounds was accomplished in 1h after sample receipt. This methodology has been successfully applied to the analysis of cattle and pig tissue samples from local markets and slaughterhouses of the Valencian Community (Spain). The results showed the presence of some antimicrobials at different concentrations. Quinolones and tetracyclines were the antimicrobials most detected in cattle and pig samples, respectively. Sulfonamides were also frequently detected in both types of samples.     

A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization

Molecular Diversity - A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the...