RESUMEN
α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds' effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome.
Asunto(s)
Antioxidantes , Metabolismo Energético , Inhibidores de Glicósido Hidrolasas , Hidroquinonas , alfa-Glucosidasas , Humanos , Células CACO-2 , alfa-Glucosidasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/metabolismo , Hidroquinonas/farmacología , Hidroquinonas/química , Metabolismo Energético/efectos de los fármacos , Glucólisis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacosRESUMEN
A novel series of antitumor hybrids was synthesized using 1,4-benzohydroquinone and chalcone, furane, or pyrazoline scaffolds. This were achieved through isosteric substitution of the aryl group of the chalcone ß-carbon with the furanyl moiety and structural modification of the α,ß-unsaturated carbonyl system. The potential antitumor activity of these hybrids was evaluated in vivo on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, demonstrating cytotoxic activity with IC50 values ranging from 28.8 to 124.6 µM. The incorporation of furan and pyrazoline groups significantly enhanced antiproliferative properties compared to their analogues and precursors (VII-X), which were inactive against both neoplastic cell lines. Compounds 4, 5, and 6 exhibited enhanced cytotoxicity against both cell lines, whereas compound 8 showed higher cytotoxic activity against HT-29 cells. Molecular docking studies revealed superior free-energy values (ΔGbin) for carcinogenic pathway-involved kinase proteins, with our in silico data suggesting that these derivatives could be promising chemotherapeutic agents targeting kinase pathways. Among all the synthesized PIBHQ compounds, derivatives 7 and 8 exhibited the best drug-likeness properties, with values of 0.53 and 0.83, respectively. ADME results collectively suggest that most of these compounds hold promise as potential candidates for preclinical assays.
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Antineoplásicos , Hidroquinonas , Simulación del Acoplamiento Molecular , Pirazoles , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Hidroquinonas/química , Hidroquinonas/farmacología , Hidroquinonas/síntesis química , Células MCF-7 , Proliferación Celular/efectos de los fármacos , Chalcona/química , Chalcona/farmacología , Células HT29 , Chalconas/química , Chalconas/farmacología , Chalconas/síntesis química , Relación Estructura-Actividad , Línea Celular Tumoral , AnimalesRESUMEN
Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with ortho-carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic ortho-carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria.
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Plaquetas , Hidroquinonas , Potencial de la Membrana Mitocondrial , Compuestos Organofosforados , Inhibidores de Agregación Plaquetaria , Humanos , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Hidroquinonas/farmacología , Hidroquinonas/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/química , Fosforilación Oxidativa/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.
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Clobetasol , Quimioterapia Combinada , Hidroquinonas , Melanosis , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Hidroquinonas/administración & dosificación , Hidroquinonas/efectos adversos , Melanosis/tratamiento farmacológico , Melanosis/diagnóstico , Femenino , Método Doble Ciego , Adulto , Clobetasol/administración & dosificación , Clobetasol/efectos adversos , Persona de Mediana Edad , Dermatosis Facial/tratamiento farmacológico , Esquema de Medicación , Administración Cutánea , Resultado del Tratamiento , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversosRESUMEN
Melasma is an acquired chronic condition characterized by hyperchromic patches in photo-exposed areas. The search for new compounds for the treatment of melasma without side effects is constant. In this context, the aim of this study was to investigate the in vitro cytotoxic and antimelanogenic effects of the trace elements Zinc (Zn) and Selenium (Se). In this study, we evaluated the effects of 30 µM hydroquinone, this concentration did not alter mitochondrial function (MTT assay), but increased the percentage of necrotic cells and levels of reactive species. Furthermore, it showed no influence on tyrosinase activity and melanin content. Unlike hydroquinone, exposure for 48 h to 100 µM Zn and 1 and 5 µM Se had no significant influence on the analysis of reactive species, as well as on the percentage of necrotic cells. Still, specifically in relation to 100 µM Zn, it decreased the melanin content. Given the above, the trace elements Zn and Se did not show toxicity at the concentrations tested and Zn showed a promising effect, however, the mechanism needs to be better explored in order to contribute to new and updated research in the fight against melasma with a perspective of therapeutic use.
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Melanosis , Selenio , Oligoelementos , Humanos , Selenio/farmacología , Selenio/análisis , Zinc/análisis , Zinc/farmacología , Oligoelementos/análisis , Hidroquinonas/análisis , Melaninas , Melanosis/tratamiento farmacológicoRESUMEN
INTRODUCTION: The use of triphenylphosphonium cation (TPP+) linked to phenolic compounds by alkyl chains has a significant relevance as a mitochondrial delivery strategy in biomedicine because it affects mitochondrial bioenergetics in models of noncommunicable diseases such as cancer and cardiovascular-related conditions. Studies indicate that a long alkyl chain (10-12 carbon) increases the mitochondrial accumulation of TPP+-linked drugs. In contrast, other studies show that these compounds are consistently toxic to micromolar concentrations (as observed in platelets). In the present study, we evaluated the in vitro effect of three series of triphenylphosphonium-linked acyl hydroquinones derivates on the metabolism and function of human platelets using 3-9 carbons for the alkyl linker. Those were assessed to determine the role of the length of the alkyl chain linker on platelet toxicity. METHODS: Human platelets were exposed in vitro to different concentrations (2-40 µM) of every compound; cellular viability, phosphatidylserine exposition, mitochondrial membrane potential (ΔΨm), intracellular calcium release, and intracellular ROS generation were assessed by flow cytometry. An in silico energetic profile was generated with Umbrella sampling molecular dynamics (MD). RESULTS AND CONCLUSIONS: There was an increase in cytotoxic activity directly related to the length of the acyl chain and lipophilicity, as seen by three techniques, and this was consistent with a decrease in ΔΨm. The in silico energetic profiles point out that the permeability of the mitochondrial membrane may be involved in the cytotoxicity of phosphonium salts. This information may be relevant for the design of new TPP+ -based drugs with a safe cardiovascular profile.
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Antineoplásicos , Hidroquinonas , Humanos , Hidroquinonas/farmacología , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Antineoplásicos/farmacología , Metabolismo Energético , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/metabolismo , Potencial de la Membrana MitocondrialRESUMEN
Contributing to the development of sustainable electroanalytical chemistry, electrochemically reduced graphene oxide (ERGO) films obtained from residual graphite of discharged Zn-C batteries are proposed in this work. Graphite from the cathode of discarded Zn-C batteries was recovered and used in the synthesis of graphene oxide (GO) by the modified Hummer's method. The quality of the synthesized GO was verified using different characterization methods (FT-IR, XRD, SEM, and TEM). GO films were deposited on a glassy carbon electrode (GCE) by the drop coating method and then electrochemically reduced by cathodic potential scanning using cyclic voltammetry. The electrochemical features of the ERGO films were investigated using the ferricyanide redox probe, as well as paracetamol (PAR) and hydroquinone (HQ) molecules as model analytes. From the cyclic voltammetry assays, enhanced heterogeneous electron transfer rate constants (k0) were observed for all redox systems studied. In analytical terms, the ERGO-based electrode showed higher analytical sensitivity than the bare and GO-modified GCE. Using differential pulse voltammetry, wide linear response ranges and limits of detection of 0.14 µmol L-1 and 0.65 µmol L-1 were achieved for PAR and HQ, respectively. Furthermore, the proposed sensor was successfully applied to the determination of PAR and HQ in synthetic urine and tap water samples (recoveries close to 100%). The outstanding electrochemical and analytical properties of the proposed ERGO films are added to the very low cost of the raw material, being presented as a green-based alternative for the development of electrochemical (bio)sensors with unsophisticated resources.
Asunto(s)
Grafito , Grafito/química , Acetaminofén , Hidroquinonas , Espectroscopía Infrarroja por Transformada de Fourier , Técnicas Electroquímicas/métodos , Carbono , ZincRESUMEN
A hiperpigmentação da pele, principalmente na região facial, resulta em um incômodo estético que afeta a qualidade de vida do indivíduo, levando a busca por produtos clareadores. Este estudo avaliou a conformidade dos rótulos de cosméticos comercializados como "produtos clareadores de pele", bem como a existência de substâncias clareadoras proibidas neste tipo de produto. Foi realizada uma análise transversal descritiva qualitativa no período de abril a maio de 2022, em busca por cosméticos comercializados em estabelecimentos farmacêuticos e lojas de produtos cosméticos localizadas no município de Juazeiro/BA. Foram selecionados 18 produtos e os desvios de rotulagem identificados com base na legislação utilizada vigente à época do estudo, foram: ausência de informações sobre advertências/restrições de uso e número de registro incompleto, equivalente a 16,7% (n = 3) das amostras. A hidroquinona, proibida nesse tipo de produto, foi encontrada em um cosmético (5,5%). Embora a maioria das amostras analisadas esteja em conformidade com as exigências legais, os resultados evidenciam descumprimentos, indicando a necessidade de uma fiscalização mais rigorosa a fim de evitar possíveis danos à saúde do usuário.
Skin hyperpigmentation, particularly in the facial region, can be an aesthetic nuisance that affects an individual's quality of life, leading them to seek out whitening products. This study evaluated the compliance of cosmetics labels marketed as "skin lightening products", and assessed the presence of whitening substances prohibited in this type of product. A qualitative, descriptive, cross-sectional analysis was conducted between April and May 2022 in Juazeiro, Bahia, Brazil, focusing on cosmetics sold in pharmaceutical establishments and cosmetic product stores. Eighteen products were selected, and labeling deviations identified based on the legislation in force at the time of the study. These included a lack of information on warnings/use restrictions and incomplete registration numbers, affecting 16.7% (n = 3) of the samples. Hydroquinone, prohibited in this type of product by the legislation, was detected in one cosmetic (5.5%). Although most of the analyzed samples comply with legal requirements, the observed non-compliance highlights the need for more stringent inspection to prevent potential harm to user's health.
Asunto(s)
Hiperpigmentación/terapia , Etiquetado de Cosméticos , Preparaciones para Aclaramiento de la Piel/análisis , Hidroquinonas/toxicidad , BrasilRESUMEN
Multiple drug resistance (MDR) bacterial strains are responsible by 1.2 million of human deaths all over the world. The pathogens possess efficient enzymes which are able to mitigate the toxicity of reactive oxygen species (ROS) produced by some antibiotics and the host immune cells. Among them, the bacterial peroxiredoxin alkyl hydroperoxide reductase C (AhpC) is able to decompose efficiently several kinds of hydroperoxides. To decompose their substrates AhpC use a reactive cysteine residue (peroxidatic cysteine-CysP) that together with two other polar residues (Thr/Ser and Arg) comprise the catalytic triad of these enzymes and are involved in the substrate targeting/stabilization to allow a bimolecular nucleophilic substitution (SN2) reaction. Additionally to the high efficiency the AhpC is very abundant in the cells and present virulent properties in some bacterial species. Despite the importance of AhpC in bacteria, few studies aimed at using natural compounds as inhibitors of this class of enzymes. Some natural products were identified as human isoforms, presenting as common characteristics a bulk hydrophobic moiety and an α, ß-unsaturated carbonylic system able to perform a thiol-Michael reaction. In this work, we evaluated two chemically related natural products: 1,4-dihydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzene (C1) and 4-hydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzoic acid (C2), both were isolated from branches Piper crassinervium (Piperaceae), over the peroxidase activity of AhpC from Pseudomonas aeruginosa (PaAhpC) and Staphylococcus epidermidis (SeAhpC). By biochemical assays we show that although both compounds can perform the Michael addition reaction, only compound C2 was able to inhibit the PaAhpC peroxidase activity but not SeAhpC, presenting IC50 = 20.3 µM. SDS-PAGE analysis revealed that the compound was not able to perform a thiol-Michael addition, suggesting another inhibition behavior. Using computer-assisted simulations, we also show that an acidic group present in the structure of compound C2 may be involved in the stabilization by polar interactions with the Thr and Arg residues from the catalytic triad and several apolar interactions with hydrophobic residues. Finally, C2 was not able to interfere in the peroxidase activity of the isoform Prx2 from humans or even the thiol proteins of the Trx reducing system from Escherichia coli (EcTrx and EcTrxR), indicating specificity for P. aeruginosa AhpC.
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Peroxirredoxinas , Piper , Humanos , Peroxirredoxinas/metabolismo , Cisteína/química , Piper/química , Ácido Benzoico , Hidroquinonas , Bacterias/metabolismo , Compuestos de Sulfhidrilo , Antioxidantes , Escherichia coli/metabolismo , Peroxidasas/metabolismo , Proteínas Bacterianas/metabolismoRESUMEN
BACKGROUND: Traditional production of dry salted shrimp enhances cholesterol oxidation and astaxanthin degradation in the product. The aim of this study was to evaluate the effect of addition of the antioxidants butylhydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ) to cooked shrimp on the formation of cholesterol oxidation products (COPs) and astaxanthin degradation during solar drying of shrimp. RESULTS: The added antioxidants significantly inhibited COPs formation after the product was boiled in brine. Smaller amounts of COPs were formed in antioxidant-treated shrimps (~-23%) as compared to untreated samples. The antioxidants continued to significantly inhibit COPs formation (~-39%) during sun drying. Similarly, TBHQ and BHT reduced by 51.3% and 37.2%, respectively, the degradation rate of astaxanthin, favoring a higher retention of this carotenoid in the final product. CONCLUSION: The use of the antioxidants BHT and TBHQ in the preparation of dry salted shrimp significantly inhibited the formation of COPs after cooking raw shrimp and during direct solar drying. They also protected astaxanthin contained in the cooked shrimp from photodegradation. These results are technologically relevant because it is possible to prepare a product with a higher content of astaxanthin and lower the presence of hazardous COPs. © 2022 Society of Chemical Industry.
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Antioxidantes , Hidroquinonas , Antioxidantes/farmacología , Antioxidantes/química , ColesterolRESUMEN
Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.
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Melanosis , Protectores Solares , Femenino , Humanos , Protectores Solares/uso terapéutico , Melanosis/etiología , Tretinoina/efectos adversos , Retinoides/uso terapéutico , Fluocinolona Acetonida/efectos adversos , Hidroquinonas/uso terapéutico , Resultado del TratamientoRESUMEN
Tert-butylhydroquinone (TBHQ) is a synthetic food antioxidant with biological activities, but little is known about its pharmacological benefits in liver disease. Therefore, this work aimed to evaluate TBHQ during acute liver damage induced by CCl4 (24 h) or BDL (48 h) in Wistar rats. It was found that pretreatment with TBHQ prevents 50% of mortality induced by a lethal dose of CCl4 (4 g/kg, i.p.), and 80% of BDL+TBHQ rats survived, while only 50% of the BDL group survived. Serum markers of liver damage and macroscopic and microscopic (H&E staining) observations suggest that TBHQ protects from both hepatocellular necrosis caused by the sublethal dose of CCl4 (1.6 g/kg, i.p.), as well as necrosis/ductal proliferation caused by BDL. Additionally, online databases identified 49 potential protein targets for TBHQ. Finally, a biological target candidate (Keap1) was evaluated in a proof-of-concept in silico molecular docking assay, resulting in an interaction energy of -5.5491 kcal/mol, which was higher than RA839 and lower than monoethyl fumarate (compounds known to bind to Keap1). These findings suggest that TBHQ increases the survival of animals subjected to CCl4 intoxication or BDL, presumably by reducing hepatocellular damage, probably due to the interaction of TBHQ with Keap1.
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Hidroquinonas , Factor 2 Relacionado con NF-E2 , Animales , Ratas , Ratas Wistar , Proteína 1 Asociada A ECH Tipo Kelch , Simulación del Acoplamiento Molecular , NecrosisRESUMEN
Hydroquinone is a skin-lightening agent used as an active ingredient in topical dermatological formulations prescribed for treating cutaneous diseases caused by hyperpigmentation. Despite being widely used, some toxicological aspects have been associated with these products, mainly due to overdosage and long-term use combined with the easy oxidation of hydroquinone. In this work, an investigative study has been done to gather enough data for selecting a quantitative analytical method for quality control purposes that considers the ease of oxidation not only within the product but also during the experimental procedures. After studying the influence of pH, reversibility, sampling, and standard solution preparation on the redox reaction between hydroquinone and benzoquinone by using spectroscopic, electrophoretic, and electroanalytical measurements, a reliable, fast, and selective chronoamperometric method was achieved. The optimized method was used for the analysis of samples, previously diluted in Britton-Robinson (BR) buffer (pH 5.5) and methanol (1 : 9, v/v), by applying a potential fixed at 0.4 V. A glassy-carbon working electrode, lab-made Ag/AgCl(sat) and platinum wire as a reference electrode and auxiliary electrodes, respectively, and BR buffer (pH 5.5) as supporting electrolyte were the additional experimental conditions used. Analytical performance parameters were verified to confirm the applicability of the new method (LOD 4.22 µmol L-1 and LOQ 14.1 µmol L-1; recovery mean value of 100% with 0.22% RSD). A gel topical formulation containing 4% (w/w) hydroquinone was analyzed through the developed method for determination of dosage and oxidation traces, and a content of 3.53 ± 0.095% (w/w) was found with no indications of degradation.
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Benzoquinonas , Hidroquinonas , Electroquímica/métodos , Composición de MedicamentosRESUMEN
Bacillus subtilis is a Gram-positive bacterium with a respiratory chain embedded in the cytoplasmic membrane. The respiratory chain is bifurcated after menaquinol into a cytochrome b6c + caa3 branch and a branch with up to three quinol oxidases. The complexes that generate the proton gradient are b6c, associated with caa3 and aa3 oxidase. The b6c and caa3 complexes form a supercomplex, and it is proposed to form respiratory strings in the membrane. There is still information missing about the quinol branch and if the primary oxidase quinol aa3 is associated with the electron donor complexes. It is unclear whether succinate quinone reductase (SQR) can form associations with the quinol branch or the cytochrome branch. In this paper, we show the separation of an almost pure b6c complex associated with cytochromes c550 and c551. We obtained a b6c + caa3 supercomplex of 600 kDa and SQR, aa3, and NADH dehydrogenase by dodecyl maltoside solubilization and separation of the respiratory chain components by ionic exchange chromatography. We found that aa3 does not associate with other complexes. SQR was associated with the b6c complex in a mutant lacking aa3. This association could facilitate electron transfer from SQR to menaquinone-7. The lack of associations between the abundant quinol oxidase aa3 and other complexes is a feature we cannot explain yet.
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Bacillus subtilis , Hidroquinonas , Transporte de Electrón , Complejo II de Transporte de ElectronesRESUMEN
The development of a homemade carbon black composite filament with polylactic acid (CB-PLA) is reported. Optimized filaments containing 28.5% wt. of carbon black were obtained and employed in the 3D printing of improved electrochemical sensors by fused deposition modeling (FDM) technique. The fabricated filaments were used to construct a simple electrochemical system, which was explored for detecting catechol and hydroquinone in water samples and detecting hydrogen peroxide in milk. The determination of catechol and hydroquinone was successfully performed by differential pulse voltammetry, presenting LOD values of 0.02 and 0.22 µmol L-1, respectively, and recovery values ranging from 91.1 to 112% in tap water. Furthermore, the modification of CB-PLA electrodes with Prussian blue allowed the non-enzymatic amperometric detection of hydrogen peroxide at 0.0 V (vs. carbon black reference electrode) in milk samples, with a linear range between 5.0 and 350.0 mol L-1 and low limit of detection (1.03 µmol L-1). Thus, CB-PLA can be successfully applied as additively manufactured electrochemical sensors, and the easy filament manufacturing process allows for its exploration in a diversity of applications.
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Hidroquinonas , Hollín , Catecoles/análisis , Peróxido de Hidrógeno , Hidroquinonas/análisis , Poliésteres , AguaRESUMEN
Methyl parathion is an organophosphorus pesticide widely employed worldwide to control pests in agricultural and domestic environments. However, due to its intensive use, high toxicity, and environmental persistence, methyl parathion is recognized as an important ecosystem and human health threat, causing severe environmental pollution events and numerous human poisoning and deaths each year. Therefore, identifying and characterizing microorganisms capable of fully degrading methyl parathion and its degradation metabolites is a crucial environmental task for the bioremediation of pesticide-polluted sites. Burkholderia zhejiangensis CEIB S4-3 is a bacterial strain isolated from agricultural soils capable of immediately hydrolyzing methyl parathion at a concentration of 50 mg/L and degrading the 100% of the released p-nitrophenol in a 12-hour lapse when cultured in minimal salt medium. In this study, a comparative proteomic analysis was conducted in the presence and absence of methyl parathion to evaluate the biological mechanisms implicated in the methyl parathion biodegradation and resistance by the strain B. zhejiangensis CEIB S4-3. In each treatment, the changes in the protein expression patterns were evaluated at three sampling times, zero, three, and nine hours through the use of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), and the differentially expressed proteins were identified by mass spectrometry (MALDI-TOF). The proteomic analysis allowed the identification of 72 proteins with differential expression, 35 proteins in the absence of the pesticide, and 37 proteins in the experimental condition in the presence of methyl parathion. The identified proteins are involved in different metabolic processes such as the carbohydrate and amino acids metabolism, carbon metabolism and energy production, fatty acids ß-oxidation, and the aromatic compounds catabolism, including enzymes of the both p-nitrophenol degradation pathways (Hydroquinone dioxygenase and Hydroxyquinol 1,2 dioxygenase), as well as the overexpression of proteins implicated in cellular damage defense mechanisms such as the response and protection of the oxidative stress, reactive oxygen species defense, detoxification of xenobiotics, and DNA repair processes. According to these data, B. zhejiangensis CEIB S4-3 overexpress different proteins related to aromatic compounds catabolism and with the p-nitrophenol degradation pathways, the higher expression levels observed in the two subunits of the enzyme Hydroquinone dioxygenase, suggest a preferential use of the Hydroquinone metabolic pathway in the p-nitrophenol degradation process. Moreover the overexpression of several proteins implicated in the oxidative stress response, xenobiotics detoxification, and DNA damage repair reveals the mechanisms employed by B. zhejiangensis CEIB S4-3 to counteract the adverse effects caused by the methyl parathion and p-nitrophenol exposure.
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Dioxigenasas , Metil Paratión , Plaguicidas , Aminoácidos , Burkholderiaceae , Carbohidratos , Carbono , Ecosistema , Ácidos Grasos , Hidroquinonas/análisis , Metil Paratión/análisis , Metil Paratión/química , Metil Paratión/toxicidad , Nitrofenoles , Compuestos Organofosforados , Proteómica , Especies Reactivas de Oxígeno , SueloRESUMEN
The capacity to generate a constant signal response from an enzyme on an electrode surface has been a fascinating topic of research from the past three decades. To nourish the enzymatic activity during electrochemical reactions, the immobilization of dual enzymes on the electrode surface could prevent the enzymatic loss without denaturation and thus long-term stability can be achieved. For effective immobilization of dual enzymes, mesoporous materials are the ideal choice because of its numerous advantages such as 1. The presence of porous structure facilitates high loading of enzymes 2. The formation of protective environment can withstand the enzymatic activity even at acidic or basic pH values and even at elevated temperatures. Herein, we develop bienzymatic immobilization of horseradish peroxidase (HRP) and cholesterol oxidase (ChOx) on mesoporous V2O5-TiO2 based binary nanocomposite for effective sensing of hydrogen peroxide (H2O2) in presence of redox mediator hydroquinone (HQ). The utilization of redox mediator in second-generation biosensing of H2O2 can eliminate the interference species and reduces the operating potential with higher current density for electrochemical reduction reaction. Using this mediator transfer process approach at HRP/ChOx/V2O5-TiO2 modified GC, the H2O2 can be determined at operating potential (-0.2 V) with good linear range (0.05-3.5 mM) higher sensitivity (1040 µAµM-1 cm-2) and lower detection limit of about 20 µM can be attained, which is due to higher mediation of electrons were transferred to the enzyme cofactors. These interesting characteristics could be due to mesoporous structure of V2O5-TiO2 can induce large immobilization and facilitate higher interaction with enzymes for wide range of biosensing applications.
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Técnicas Biosensibles , Peróxido de Hidrógeno , Colesterol Oxidasa , Coenzimas , Enzimas Inmovilizadas/química , Peroxidasa de Rábano Silvestre/química , Peróxido de Hidrógeno/química , Hidroquinonas , TitanioRESUMEN
The asymmetric total synthesis of angucycline antibiotics (S)-brasiliquinones B and C was accomplished. The benz[a]anthraquinone core was constructed via oxidative cyclization of a hydroquinone-silyl enol ether hybrid. The resultant pentacyclic acetal was converted to the silyl enol ether, which was treated with Pd(II)/O2 to afford brasiliquinone C, after multistep conversion including dehydrogenation, desilylation and deacetalization, and hydroquinone oxidation. The (S)-configuration of natural brasiliquinones was confirmed based on the stereochemical correlation with the synthetic products.
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Acetales , Éter , Alcoholes , Antraquinonas , Antibacterianos , Ciclización , Éteres , Éteres de Etila , Hidroquinonas , Estructura Molecular , Estrés Oxidativo , EstereoisomerismoRESUMEN
The present study reports the synthesis and characterization of hydrophobic deep eutectic solvents (HDES) based on fatty acids and tetrabutylammonium bromide (TBAB) or 1-octanol using Fourier transform infrared spectroscopy, and the analysis of the physicochemical properties (viscosity, density, electrical conductivity, and water content) of these solvents. A carbon paste electrode modified with 6.0% (m/m) decanoic acid and TBAB-based HDES was characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy. The oxidation peak currents of the proposed electrode were enhanced by its high electrochemical activity, fast electron transfer rate, and high surface area, while a remarkable decrease was observed in the peak potential separation. The electrochemical determination of hydroquinone (H2Q) was carried out using square-wave adsorptive anodic stripping voltammetry (SWAdASV). The electrode response was found to be linear in the H2Q concentration range of 2.5 × 10-6-3.0 × 10-3 mol L-1, with the limit of detection (LOD) of 7.7 × 10-7 mol L-1. The method was successfully applied for H2Q determination in dermatological creams.
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Carbono , Hidroquinonas , Carbono/química , Disolventes Eutécticos Profundos , Técnicas Electroquímicas/métodos , Electrodos , Hidroquinonas/análisis , SolventesRESUMEN
A sensitive detection of carbohydrate antigen 15-3 (CA15-3) levels may allow for early diagnosis and monitoring the treatment of breast cancer, but this can only be made in routine clinical practice if low-cost immunosensors are available. In this work, we developed a sandwich-type electrochemical immunosensor capable of rapid detection of CA15-3 with an ultra-low limit of detection (LOD) of 0.08 fg mL-1 within a wide linear concentration range from 0.1 fg mL-1 to 1 µg mL-1. The immunosensor had a matrix of a layer-by-layer film of Au nanoparticles and reduced graphene oxide (Au-rGO) co-electrodeposited on screen-printed carbon electrodes (SPCE). The high sensitivity was achieved by using secondary antibodies (Ab2) labeled with horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2) as signal amplifiers, and hydroquinone (HQ) was used as an electron mediator. The immunosensor was selective for CA15-3 in human serum and artificial saliva samples, robust, and stable to permit storage at 4 °C for more than 30 days. With its high performance, the immunosensor may be incorporated into future point-of-care (POC) devices to determine CA15-3 in distinct biological fluids, including in blood and saliva samples.