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In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders. [ABSTRACT FROM AUTHOR]

Different starch properties may cause alterations in the foodstuff's external appearance. However, modification processes in starches are usually secretive. The use of chemically modified starches is regulated by international standards, which makes it important to identify its presence and type. Mid-infrared spectroscopy (MIR)-modified starches' identification can be hindered by the presence of excess glucose. This research investigates types of modification in commercial starches and in approaches that circumvent MIR's limitations with exploratory analysis. It also considers that enzymatic hydrolysis (α-amylase and amyloglucosidase) can highlight the points of modification in the structure, which can be detected with infrared assays. To determine if sour cassava starch (FCS) is modified and check its type, six samples were selected: a native one, three of the most common cassava modified starches (etherified, esterified, and FCS), and two laboratory processed samples (Acid, Oxidized). The results showed that the sour cassava starch showed similarities with a commercial ester and an oxidized cassava starch, which may be due to the formation of a graft, corresponding to what the literature has already reported for corn starch treated with lactic acid and gamma radiation. [ABSTRACT FROM AUTHOR]

Abstract: The electrochemical behaviour of the spice biomarkers, curcumin and capsaicin, two polyphenolic compound with a large spectrum of medical application, has been studied by cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The oxidation of curcumin is an irreversible process that in acidic and mild alkaline supporting electrolytes proceeds in two steps. The first irreversible oxidation step leads to the formation of a catechol moiety, and the second reversible step occurs for a higher potential. The oxidation mechanism of ferulic acid, capsaicin and dihydrocapsaicin, curcumin chemical analogues was also investigated. The oxidation of ferulic acid is similar to curcumin whereas the oxidation of capsaicin and dihydrocapsaicin led to the formation of only one oxidation product. A redox mechanism for curcumin oxidation has been proposed. [Copyright &y& Elsevier]

A new approach using paper spray ionization mass spectrometry (PSI–MS) for the analysis of steroid hormones in wastewater samples has been demonstrated. Triangular papers containing paraffin barriers as microfluidic channels were used to direct the sample solution to the paper tip, preventing the sample from spreading over the corners of the paper. The method was used to analyze the hormones levonorgestrel and algestone acetophenide in industrial wastewaters. Analytical curves presented a correlation coefficient (R2) above 0.99. Limits of quantification were below 2.3 ppm and limits of detection below 0.7 ppm. Values of precision (coefficient of variation) and accuracy (relative error) were less than 15% for all analyses. Recovery results ranged from 82% to 102%. Levonorgestrel was also analyzed by high-performance liquid chromatography coupled to mass spectrometry in order to compare the analytical performance with PSI–MS. No statistically significant differences were found between both methods. This study demonstrates the usefulness of PSI–MS for rapid analysis of hormones in industrial wastewater samples and also indicates its potential to be employed as a simple and reliable analytical method in environmental sciences. [ABSTRACT FROM AUTHOR]

Bioremediation is a strategy to mitigate environmental impacts of hazardous pollutants from anthropogenic sources. Natural byproducts, including agroindustrial wastes (AW) can be used to induce enzyme biosynthesis, leading up to enhancement of pollutants degradation process. Therefore, this study aimed to evaluate the use of cupuaçu, Theobroma grandiflorum AW as Pycnoporus sanguineus Laccase (Lac) inducer in order to promote 17-α-ethinylestradiol (EE2) bioremediation. The macro and micro-nutrients levels of cupuaçu AWs were evaluated in order to establish further correlations with enzymatic biosynthesis induction. The fungus was cultivated for 7 days in temperature of 28 ± 2 °C and agitation of 150 rpm. For bioremediation, Lac enzymatic extract was added to EE2 solution (10 µg mL−1) and the percentage of removal was evaluated by HPLC after 1-24 hr of reaction. At optimized conditions, the enzyme extract production was remarkably enhanced by adding only 1% (w/v) of cupuaçu AW. Lac activity reached 1642 U mL−1 on the 6th day of culture, which was higher than positive control (511 U mL−1). 86% of EE2 removal was reached after 4 hr, and after 8 hr of reaction, 96.5% was removed. Analysis by direct infusion in MS-ESI-TOF exhibited intermediary compounds formed by radical hydroxilation. [ABSTRACT FROM AUTHOR]

Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This research aimed to design, synthesis and to evaluate the anti-inflammatory and antinociceptive effects of the new compound, which is derived from nimesulide and darbufelone lead compounds. The new dual inhibitor 5-LOX/COX has the possible advantage of gastrointestinal safety. A voltammetric experiment was conducted to observe the drug's antioxidative effect. A formalin test, a hot plate test and carrageenan-induced mechanical hyperalgesia were employed to evaluate the analgesic nature of LQFM-091. To evaluate anti-inflammatory activity, we measured edema, leukocyte count, myeloperoxidase activity and cytokines levels in carrageenan-induced inflammation tests. We elucidated the underlying mechanisms by assessing the interaction the with COXs and LOX enzymes by colorimetric screening assay and molecular docking. The lethal dose (LD 50 ) was estimated using 3T3 Neutral Red Uptake assay. Our results indicate that the LQFM-091 prototype is a powerful antioxidant, as well as able to inhibit COX-1, COX-2 and LOX activities. LQFM091 was classified in GHS category 4 (300 < LD 50 < 2000 mg/Kg). This prototype showed analgesic activity in the formalin test and decreased carrageenan-induced mechanical hyperalgesia. Furthermore, LQFM-091 reduced the paw edema induced by carrageenan and reduced the leukocyte count, myeloperoxidase activity, TNF-α and IL-1β levels in the pleural exudate. Another interesting finding was the absence of gastrointestinal lesions. These data indicate that LQFM-091 produced antinociceptive and anti-inflammatory effects while maintaining gastrointestinal safety. Furthermore, this compound presented a safe toxicological profile. Blocked COXs and LOX enzymes are important targets for manipulating the mechanism of this compound. [ABSTRACT FROM AUTHOR]

A new strategy for the construction of a polyphenol oxidase carbon paste biosensor for paracetamol detection is reported. The eggplant (Solanum melongena) was processed to collect the polyphenol oxidase as an enzyme that was incorporated in the carbon paste sensor construction. The constructed sensor displayed high sensitivity and good selection for paracetamol detection and recognition. Optimized conditions included pH 6.0 (highest activity), pH 7.0 (highest stability), pulse amplitude of 50 mV, and 15% of vegetable extract per carbon paste. The sensor displayed a linear range from 20 to 200 µM, with a detection limit of 5 µM. Application of the sensor to paracetamol determination in tablet and oral solutions have shown satisfactory results. The efficiency of the method showed very good repeatability ranging between 1.26 and 1.72% relative standard deviation for interday analysis, while recoveries for paracetamol varied between 97.5 and 99.8% for the voltammetric determination. The strategy for a simple, low cost, and efficient eggplant polyphenol oxidase sensor showcased in this work provides an opportunity for the detection of other phenolic compounds in various matrices. [ABSTRACT FROM AUTHOR]

Oxidative stress, impaired antioxidant defense and neuroinflammation are often associated with the onset and progression of neuropsychiatric diseases. Conversely, several piperazine compounds presents beneficial neuropharmacological effects as well as antioxidant activity, and some derivatives combine both activities. LQFM212 (2,6-di- tert -butyl-4-((4-(2-hydroxyethyl)piperazin-1- yl)methyl)phenol) was synthesized to produce effects on CNS and to have an additional antioxidant effect. Previous preclinical tests have been shown anxiolytic- and antidepressant-like effects of LQFM212 in mice. Herein, the main objective was to verify the possible antioxidant potential and the effects of LQFM212 against behavioral changes, inflammatory and oxidative markers induced by lipopolysaccharide (LPS). Initially, antioxidant potential of LQFM212 was evaluated by electrochemical assays. Afterwards, the effects of oral treatment with LQFM212 were evaluated in mice using LPS-induced models of systemic or local inflammation. In LPS-induced neuroinflammation, LQFM212 treatment reverted changes caused by LPS, demonstrated by attenuated anxiogenic- and depressive-like behaviors, reduced pro-inflammatory cytokines (TNF-α and IL-1β) and increased anti-inflammatory cytokines (IL-4 and IL-10) on serum, and also improved oxidative stress-related changes (levels of nitrite, malondialdehyde, glutathione and carbonylated protein, and superoxide dismutase, catalase, myeloperoxidase and cholinesterase activities) on brain cortex and hippocampus. However, LQFM212 treatment did not attenuate the inflammatory changes in LPS-induced pleurisy model. LQFM212 presents antioxidant activity and ameliorates behavioral, inflammatory and oxidative changes after LPS-induced neuroinflammation model. These effects do not seem to be secondary to a peripheral anti-inflammatory action of LQFM212, since this compound failed to attenuate the inflammatory changes in LPS-induced pleurisy model. [ABSTRACT FROM AUTHOR]

This study’s aim was to determine the effect of hydroalcoholic extract of M. cauliflora (HEMC) on vascular tension and blood pressure in rats. In our in vitro studies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic and β-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In our in vivo studies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness. [ABSTRACT FROM AUTHOR]

The current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)−4-((1-phenyl-1 H -pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)− 1 H -pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 µmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 µmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT 1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT 1A receptor with a moderate affinity (K i around 5–9 µM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD 50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT 1A receptors. [Display omitted] • LQFM005 is a new phenylpiperazine derivative. • LQFM005 has a hydroxylated metabolite: LQM235. • Both compounds have anxiolytic- and antidepressant-like effects in mice. • In vivo and bindings assays suggest 5-HT 1A receptor involvement on these activities. • The compounds showed pharmacological safety and antioxidant profile. [ABSTRACT FROM AUTHOR]

The binding between anticancer drugs and double-stranded DNA (dsDNA) is a key issue to understand their mechanism of action, and many chemical methods have been explored on this task. Molecular docking techniques successfully predict the affinity of small molecules into the DNA binding sites. In turn, various DNA-targeted drugs are electroactive; in this regard, their electrochemical behavior may change according to the nature and strength of interaction with DNA. A carbon paste electrode (CPE) modified with calf thymus ds-DNA (CPDE) and computational methods were used to evaluate the drug–DNA intercalation of doxorubicin (DOX), daunorubicin (DAU), idarubicin (IDA), dacarbazine (DAR), mitoxantrone (MIT), and methotrexate (MTX), aiming to evaluate eventual correlations. CPE and CPDE were immersed in pH 7 0.1 mM solutions of each drug with different incubation times. As expected, the CPDE response for all DNA-targeted drugs was higher than that of CPE, evidencing the drug–DNA interaction. A peak current increase of up to 10-fold was observed; the lowest increase was seen for MTX, and the highest increase for MIT. Although this increase in the sensitivity is certainly tied to preconcentration effects of DNA, the data did not agree entirely with docking studies, evidencing the participation of other factors, such as viscosity, interfacial electrostatic interactions, and coefficient of diffusion. [ABSTRACT FROM AUTHOR]

This study presents a new polymeric and multielectronic system, the poly-Alizarin Red S (PARS), obtained from the electropolymerization of Alizarin Red S (ARS) dye on an edge-plane pyrolytic graphite electrode (EPPGE) surface. During EPPGE/PARS electrochemical characterization, we identified seven stable and reversible redox peaks in acidic medium (0.10 mol L−1, pH 1.62 KH 2 PO 4), which indicated its mechanisms underlying electropolymerization and electrochemical behavior. To the best of our knowledge, this is the first study to use an EPPGE/PARS electrode to detect oxandrolone (OXA) in artificial urine, where PARS acts as a synthetic receptor for OXA. The interactions of OXA with EPPGE/PARS as well as the properties of PARS were investigated using density functional theory (DFT). Atomic force microscopy (AFM) was used to characterize EPPGE/PARS, and it was found that the PARS polymer formed a semi-globular phase on the EPPGE surface. The limit of detection for OXA found by the sensor was close to 0.50 nmol L−1, with a recovery rate of approximately 100% in artificial urine. In addition to the application proposed in this study, EPPGE/PARS is a low-cost product that could be applied in several devices and processes, such as supercapacitors and electrocatalysis. • Poly-Alizarin Red S (PARS) as a polymeric and multielectronic system. • Mechanisms of electropolymerization and redox behavior of PARS. • Oxandrolone (OXA) hormone and its interactions with PARS. • Use of PARS for oxandrolone sensing in urine at low concentrations. [ABSTRACT FROM AUTHOR]

• Starch content of turmeric samples influences the spectroscopic data. • Turmeric samples can classified by adulteration with K-means of infrared spectra. • Electroanalysis show potentially lesser antioxidant capacity in adulterated samples. • 50.48 g starch per 100 g turmeric is the found threshold for adulteration. • Partial least squares regression determined starch content of turmeric. [ABSTRACT FROM AUTHOR]

Carvedilol (CRV) is a non-selective blocker of α and β adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions. [ABSTRACT FROM AUTHOR]

Microcystin-leucine arginine (MC-LR) is the most abundant and toxic secondary metabolite produced by freshwater cyanobacteria. This toxin has a high potential hazard health due to potential interactions with liver, kidney and the nervous system. The aim of this work was the design of a simple and environmentally friendly electrochemical system based on highly efficient nanostructured electrodes for the removal of MC-LR in tap water. Titania nanoparticles were deposited on carbon (graphite) under a simple and efficient microwave assisted approach for the design of the electrode, further utilized in the electrochemical remediation assays. Parameters including the applied voltage, time of removal and pH (natural tap water or alkaline condition) were investigated in the process, with results pointing to a high removal efficiency for MC-LR (60% in tap water and 90% in alkaline media experiments, under optimized conditions). [ABSTRACT FROM AUTHOR]