The use of green protic ionic liquids in a crystallization of isoniazid: Evaluation of physicochemical and biological properties of drug.

This study evaluated the synthesis of protic ionic liquids (PILs), 2-hydroxy ethylammonium formate (2-HEAF) and 2-hydroxy ethylammonium acetate (2-HEAA), and their applicability in the crystallization process of the active pharmaceutical ingredient isoniazid (INH) as anti-solvent. Isoniazid is an antibiotic used in the treatment of tuberculosis infections, being used as a first-line chemotherapeutic agent against Mycobacterium tuberculosis. Also, this investigation purposed to evaluate how these PILs can influence the habit, solubility, stability, and therapeutic efficiency of the obtained isoniazid crystals. The 2-HEAF and 2-HEAA PILs were easily formed in reactions between ethanolamine and carboxylic acids (formic or acetic acid) and they have no toxicity against Artemia salina. The PILs were able to crystallize isoniazid, influencing the crystal habit and size. The greatest variations in the hydrogen signals of the NH2 and NH groups of the amine and low variations in the chemical shifts of the hydrogens of the cation of the ethanolamine group from 2-HEAA and 2-HEAF, indicating that PILs establish possibly weak interactions with INH. The obtained crystals were more amorphous and showed higher solubility in water than standard INH. Also, these crystals showed therapeutic efficiency with antimycobacterial activity to inhibit the growth of Mycobacterium tuberculosis. The INH:2-HEAF degraded only 5.1 % (w/w), however, INH:2-HEAA degraded 32.8 % (w/w) after 60 days in an accelerated atmosphere. Then, the 2-HEAA and 2-HEAF were able to crystallize isoniazid, being a new application for these PILs and the used PILs influenced the characteristics of isoniazid crystals.

Synthesis, structural, characterization, antibacterial and antibiotic modifying activity, ADMET study, molecular docking and dynamics of chalcone (E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one in strains of Staphylococcus aureus carrying NorA and MepA efflux pumps.

Chalcones have an open chain flavonoid structure that can be obtained from natural sources or by synthesis and are widely distributed in fruits, vegetables, and tea. They have a simple and easy to handle structure due to the α-ß-unsaturated bridge responsible for most biological activities. The facility to synthesize chalcones combined with its efficient in combating serious bacterial infections make these compounds important agents in the fight against microorganisms. In this work, the chalcone (E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HDZPNB) was characterized by spectroscopy and electronic methods. In addition, microbiological tests were performed to investigate the modulator potential and efflux pump inhibition on S. aureus multi-resistant strains. The modulating effect of HDZPNB chalcone in association with the antibiotic norfloxacin, on the resistance of the S. aureus 1199 strain, resulted in increase the MIC. In addition, when HDZPNB was associated with ethidium bromide (EB), it caused an increase in the MIC value, thus not inhibiting the efflux pump. For the strain of S. aureus 1199B, carrying the NorA pump, the HDZPNB associated with norfloxacin showed no modulatory, and when the chalcone was used in association with EB, it had no inhibitory effect on the efflux pump. For the tested strain of S. aureus K2068, which carries the MepA pump, it can be observed that the chalcone together the antibiotic resulted in an increase the MIC. On the other hand, when chalcone was used in association with EB, it caused a decrease in bromide MIC, equal to the reduction caused by standard inhibitors. Thus, these results indicate that the HDZPNB could also act as an inhibitor of the S. aureus gene overexpressing pump MepA. The molecular docking reveals that chalcone has a good binding energies -7.9 for HDZPNB/MepA complexes, molecular dynamics simulations showed that Chalcone/MetA complexes showed good stability of the structure in an aqueous solution, and ADMET study showed that the chalcone has a good oral bioavailability, high passive permeability, low risk of efflux, low clearance rate and low toxic risk by ingestion. The microbiological tests show that the chalcone can be used as a possible inhibitor of the Mep A efflux pump.Communicated by Ramaswamy H. Sarma.

Cashew apple fiber prevents high fat diet-induced obesity in mice: an NMR metabolomic evaluation.

Dietary fiber intake plays an important role in the prevention of obesity. This study aimed at investigating the effect of cashew fiber without low molecular weight compounds (CABwc) on obesity prevention and metabolomics in a murine model of diet-induced obesity. Mice were fed a chow diet (CD), a high-fat diet (HFD) or a high-fat diet supplemented with CABwc (10%) (HFD-CABwc) for 15 weeks. The body weight, abdominal fat, serum glucose levels, insulin and lipid profiles, satiety hormones such as leptin and ghrelin, digestive enzymes such as amylase and lipase, and inflammatory mediators such as TNF-α, IL-6, and adiponectin were measured, in addition to performing serum and hepatic tissue analyses. The metabolomic analysis was based on nuclear magnetic resonance (NMR) spectroscopy of serum and feces. The effects observed with ingestion of CABwc were appetite control and prevention of hyperglycemia, hyperinsulinemia and hypertriglyceridemia, as well as the prevention of the inflammatory process and reduction of liver injury caused by the HFD. In addition, NMR evidenced the presence of SCFAs in serum and feces of mice fed with HFD-CABwc. These findings suggest that CABwc promoted satiety in mice, improving the metabolism of glucose and lipids. Positive effects of obesity prevention may be associated with SCFA production.

Evaluation of nutritional and chemical composition of yacon syrup using 1H NMR and UPLC-ESI-Q-TOF-MSE.

A complete characterization of yacon syrup was performed by analytical techniques, including NMR and UPLC-QTOF-MSE. The effect of the different stages of yacon syrup production on fructooligosaccharides (FOS) and chlorogenic acid (CGA) contents were also evaluated. As a result, in addition to higher levels of FOS and CGA, some mineral elements, such as K, Ca and P, and essential amino acids, such as tryptophan, valine, and threonine, were determined in yacon syrup. Twenty-five compounds were putatively identified, and the main compounds were phenolics derived from quinic and trans-cinnamic acids. Considering the different stages of yacon syrup production, the results indicate that the contents of FOS and CGA were maintained in the pulping, enzymatic maceration and microfiltration, leading to a concentration of these components in the last stage of processing (vacuum concentration). These results will be used to fortify this innovative and promising product in the area of functional foods.

Pretreatment of cashew apple bagasse using protic ionic liquids: Enhanced enzymatic hydrolysis.

To enhance the enzymatic digestibility of cashew apple bagasse (CAB) feedstock in order to produce sugar fermentation-derived bioproducts, the CAB was subjected to three different pretreatments with the ionic liquid 2-hydroxyl-ethylammonium acetate (2-HEAA) and characterized by FTIR, NMR and chemical methods. All conditions were able to delignify CAB, however the best lignin removal (95.8%) was achieved through the method performed with 8.7% w/w of CAB/2-HEAA ratio at 130°C for 24h. Although the cellulose crystallinity has been increased in CAB treated with the ionic liquid, but this fact did not influence its digestibility. Nevertheless, the pretreatment with 2-HEAA enhanced significantly the cellulose digestibility, increasing the glucose yield from 48 to 747.72mgglucose/gCAB. Furthermore, 2-HEAA pretreatment was efficient even with reused ionic liquid, obtaining high glucose concentration.