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This study introduces an innovative approach for quantifying isomeric pollutants utilizing an amperometric sensor. The determination of the isomers hydroquinone and catechol is based on the use of a glassy carbon electrode modified with Cu@PtPd/C nanoparticles (Cu@PtPd/C/GCE) in core-shell form, showing significant electrocatalytic activity in the oxidation of the later compounds. The determination was carried out at two different potentials: one at which where only hydroquinone is oxidized, and another in which where both hydroquinone and catechol are oxidized. Using these potentials, two calibration curves were built, one for the quantification of hydroquinone and the other for both isomers. Subsequently, the quantification of catechol was performed using a strategy based on the calculation of a difference using the information collected in the first step. The experiments using hydrogen peroxide as a redox probe demonstrate a clear synergistic effect in the catalytic reduction of hydrogen peroxide at -0.100 V, when Pt, Pd and Cu are incorporated into the core-shell nanostructure. The best performance was achieved with Cu@PtPd/C/GCE 1.00 mg mL-1. For the selected sensor, the analytical parameters are very competitive compared to similar devices reported in recent years for hydroquinone and catechol, with comparable linearity ranges of 0.010-0.200 mmol L-1 (hydroquinone) and 0.005-0.500 mmol L-1 (catechol), low limits of detection (LODs) of 14.0 nmol L-1 (S/N = 3.3) and 1.75 nmol L-1 (S/N = 3.3) for hydroquinone and catechol. The resulting sensor platform has been successfully applied for the quantification of hydroquinone and catechol in river and tap water and could be a promising candidate for environmental monitoring and drinking water safety.
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Background: Nicotinamide has demonstrated efficacy in the treatment of melasma. Topical antioxidants and humectants may enhance its performance. Currently, there is no controlled trial on the combination of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid, a dermo-cosmetic compound, in comparison to 4% hydroquinone for the treatment of melasma. This study aimed to explore the tolerability and efficacy of the association of the combined product versus hydroquinone. Methods: A randomized, double-blind trial involving women with facial melasma was conducted. Participants were instructed to apply the combined product (NIC group) twice daily or 4% hydroquinone for 60 days (HQ group) at night and placebo in the morning. Evaluations were performed at inclusion, after 14 and 60 days of treatment, measuring the modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life Scale (MELASQoL), and colorimetric luminosity. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. Results: Both interventions led to a progressive improvement in mMASI, MELASQoL, and GAIS, without a difference between them on D14 and D60 (p>0.2). For NIC, the mean reduction (95% CI) in mMASI was 16% (8-24%) on D14 and 32% (23-41%) on D60, while for HQ, it was 10% (7-24%) on D14 and 43% (34-52%) on D60. Reduction in colorimetric luminosity was greater in the HQ group at D60 (p=0.01). No serious side effects were identified. Of the initially included 50 patients, one was lost to follow-up in the HQ group on D60, and one withdrew consent from the NIC group, both unrelated to treatment. Conclusion: The association of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid was safe and well-tolerated, although its overall clinical efficacy was numerically inferior to 4% hydroquinone. This regimen can be considered for patients with poor tolerability to hydroquinone. Clinical Trial Registration: #RBR-4mkfmr8.
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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
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
Introducción: El melasma facial consiste en una hiperpigmentación que se origina por un incremento de la melanina epidérmica o dérmica, o ambas, y se localiza en las áreas fotoexpuestas, lo cual afecta, en ocasiones, la autoestima de hombres y mujeres. Objetivo: Evaluar la efectividad del tratamiento con láser de helio-neón en pacientes con melasma facial. Métodos: Se realizó un estudio cuasiexperimental de intervención terapéutica en 34 pacientes con diagnóstico clínico y dermatoscópico de melasma facial, atendidos en la consulta de dermatología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso en Santiago de Cuba, de enero del 2019 a igual mes del 2020, para lo cual se conformaron dos grupos: uno de estudio, que recibió tratamiento con láser, y el otro de control, tratado con crema de hidroquinona a 2 %. La información fue procesada y resumida en valores absolutos y porcentaje; asimismo, se utilizó la prueba paramétrica de homogeneidad de la Χ2, con un nivel de significación α=0,05. Resultados: En general, la mayoría de los pacientes correspondieron al grupo etario de 39-48 años (35,3 %) y al sexo femenino (82,3 %), tenían color de la piel mestizo (76,5 %) y lesiones de tamaño mediano (58,8 %). Si bien no existieron diferencias estadísticamente significativas entre las respuestas terapéuticas de cada grupo de estudio, en los pacientes tratados con láser de helio-neón la mejoría clínica fue evidente a los 3 meses de finalizada la intervención (70,6 %). Conclusiones: El tratamiento con láser de helio-neón fue efectivo en los pacientes con melasma.
Introduction: Melasma is a hyperpigmentation caused by an increase in epidermal or dermal melanin concentration, or both, and it is located on photoexposed cutaneous regions. It affects sometimes men's and women's self-esteem. Objective: To evaluate the effectiveness of helium-neon laser treatment in patients with melasma. Methods: A quasi-experimental study of therapeutic intervention in 34 patients with clinical and dermoscopic diagnosis of melasma, who were assisted at the Dermatology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba was carried out from January, 2019, to the same month in 2020, for which two groups were formed: the study group, that received laser treatment, and the control group, treated with 2% hydroquinone cream. The information was processed and expressed in absolute values and percentage; likewise, the Χ2 test for homogeneity was used, with a significance level of α=0.05. Results: In general, most of the patients belonged to 39-48 age group (35.3%) and were female (82.3%), with mixed skin color (76.5%) and medium-sized lesions (58.8%). Although there were no statistically significant differences between the therapeutic responses of each study group, clinical improvement in patients treated with helium-neon laser was evident 3 months post-intervention (70.6%). Conclusions: Helium-neon laser treatment was effective in patients with melasma.
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An electrochemical sensor based on electrochemically reduced graphene oxide (ErGO), carboxylated carbon nanotubes (cMWCNT), and gold nanoparticles (AuNPs) (GCE/ErGO-cMWCNT/AuNPs) was developed for the simultaneous detection of dihidroxybenzen isomers (DHB) hydroquinone (HQ), catechol (CC), and resorcinol (RS) using differential pulse voltammetry (DPV). The fabrication and optimization of the system were evaluated with Raman Spectroscopy, SEM, cyclic voltammetry, and DPV. Under optimized conditions, the GCE/ErGO-cMWCNT/AuNPs sensor exhibited a linear concentration range of 1.2-170 µM for HQ and CC, and 2.4-400 µM for RS with a detection limit of 0.39 µM, 0.54 µM, and 0.61 µM, respectively. When evaluated in tap water and skin-lightening cream, DHB multianalyte detection showed an average recovery rate of 107.11% and 102.56%, respectively. The performance was attributed to the synergistic effects of the 3D network formed by the strong π-π stacking interaction between ErGO and cMWCNT, combined with the active catalytic sites of AuNPs. Additionally, the cMWCNT provided improved electrocatalytic properties associated with the carboxyl groups that facilitate the adsorption of the DHB and the greater amount of active edge planes. The proposed GCE/ErGO-cMWCNT/AuNPs sensor showed a great potential for the simultaneous, precise, and easy-to-handle detection of DHB in complex samples with high sensitivity.
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Derivados del Benceno/análisis , Monitoreo del Ambiente , Grafito/química , Nanotubos de Carbono/química , Catálisis , Catecoles , Técnicas Electroquímicas , Electrodos , Oro , Hidroquinonas , Límite de Detección , Nanopartículas del Metal , Nanocompuestos , ÓxidosRESUMEN
Lipopeptides are important secondary metabolites produced by microbes. They find applications in environmental decontamination and in the chemical, pharmaceutical and food industries. However, their production is expensive. In the present work we propose three strategies to lower the production costs of surfactin. First, the coproduction of surfactin and arginase in a single growth. Second, extract the fraction of surfactin that adsorbs to the biomass and is removed from the growth medium through centrifugation. Third, use microbial biomass for the remediation of organic and inorganic contaminants. The coproduction of surfactin and arginase was evaluated by factorial design experiments using the LB medium supplemented with arginine. The best conditions for surfactin production were 22 h of growth at 37 °C using LB supplemented with arginine 7.3 g/L. Almost similar conditions were found to produce highest levels of arginase, 24 h and 6.45 g/L arginine. Decontamination of phenol and copper from artificial samples was attained by treatment with residues from lipopeptide production. Thus, cell suspensions and wash-waters used to extract surfactin from the biomass. Cell suspensions were used to successfully remove hydroquinone. Cell suspensions and wash-waters containing surfactin were successfully used to recover copper from solution. Specific monitoring methods were used for phenol and metal solutions, respectively a biosensor based on tyrosinase and either atomic absorption flame ionization spectrometry or absorbance coupled to the Arduino™ platform. Therefore, we report three alternative strategies to lower the production costs in lipopeptide production, which include the effective recovery of copper and phenol from contaminated waters using residues from surfactin production. Sustainable and profitable production of surfactin can be achieved by a coproduction strategy of lipopeptides and enzymes. Lipopeptides are collected in the supernatant and enzymes in the biomass. In addition, lipopeptides that coprecipitate with biomass can be recovered by washing. Lipopeptide wash-waters find applications in remediation and cells can also be used for environmental decontamination.
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Arginasa/biosíntesis , Bacillus/enzimología , Bacillus/crecimiento & desarrollo , Bacillus/metabolismo , Lipopéptidos/biosíntesis , Péptidos Cíclicos/biosíntesis , Bacillus/genética , Proteínas Bacterianas/biosíntesis , Biomasa , Reactores Biológicos , Cobre/metabolismo , Medios de Cultivo , ADN Bacteriano , Microbiología Ambiental , Restauración y Remediación Ambiental , Hidroquinonas/metabolismo , Fenol/metabolismoRESUMEN
INTRODUCTION: Arbutin is a phenol glucoside found in high concentrations in bearberry leaves and associated with the antimicrobial activity of the plant. Hydroquinone can also be found in leaves or be formed by degradation of arbutin. Lengthy exposure to free hydroquinone is associated with induction of toxicity in different organs. OBJECTIVE: To develop and validate a stability-indicating method by high-performance liquid chromatography diode array detector (HPLC-DAD) for simultaneous quantification of arbutin and hydroquinone in bearberry leaves and perform a comprehensive forced degradation study comparing synthetic arbutin and the arbutin in bearberry leaves. METHODS: Separation was performed using a C18 column, mobile phase with water-methanol (95:5), flow rate 1.0 mL/min and detection at 280 nm. Bearberry leaves were assayed and a forced degradation study of arbutin was performed in different conditions. RESULTS: The method complied with all required validation parameters. Contents varied from 1.19 to 4.15% (w/w) of arbutin and from 0.022 to 0.604% (w/w) of hydroquinone. Synthetic arbutin was susceptible to acid hydrolysis and oxidative degradation, forming hydroquinone as the main degradation product. The same study using bearberry leaves showed that constituents of the plant matrix may act as antioxidants, reducing the oxidative degradation of arbutin, however acid hydrolysis of arbutin occurred in higher intensity. CONCLUSION: Analysis of bearberry leaves evidenced high variation in arbutin and hydroquinone levels, demonstrating the need for standardisation and control. The stability profiles of synthetic arbutin and the arbutin in bearberry leaves were considerably different and the results may be useful for determining the most appropriate conditions for extraction and production of bearberry-based formulations.
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Arctostaphylos , Arbutina , Cromatografía Líquida de Alta Presión , Extractos Vegetales , Hojas de la PlantaRESUMEN
Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 µM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial ß-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.
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Antineoplásicos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Hidroquinonas/química , Fosforilación Oxidativa/efectos de los fármacos , Sulfonamidas/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Hidroquinonas/farmacología , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evidence on the antiplatelet activity of hydroquinones carrying electron attractor groups. In this work, we evaluate the antiplatelet effect of a series of ortho-carbonyl hydroquinone derivatives on cytotoxicity and function of human platelets, using collagen and thrombin receptor activator peptide 6 (TRAP-6) as agonists. Our structure-activity relationship study shows that gem-diethyl/methyl substitutions and the addition/modifications of the third ring of ortho-carbonyl hydroquinone scaffold influence on the selective index (IC50 TRAP-6/IC50 Collagen) and the inhibitory capacity of platelet aggregation. Compounds 3 and 8 inhibit agonist-induced platelet aggregation in a non-competitive manner with IC50 values of 1.77 ± 2.09 µM (collagen) and 11.88 ± 4.59 µM (TRAP-6), respectively and show no cytotoxicity. Both compounds do not affect intracellular calcium levels and mitochondrial bioenergetics. Consistently, they reduce the expression of P-selectin, activation of glycoprotein IIb/IIIa, and release of adenosine triphosphate and CD63 from platelet. Our findings may be used for further development of new drugs in platelet-related thrombosis diseases.
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Colágeno/farmacología , Hidroquinonas/farmacología , Fragmentos de Péptidos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno/química , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Hidroquinonas/síntesis química , Hidroquinonas/química , Estructura Molecular , Fragmentos de Péptidos/química , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Relación Estructura-ActividadRESUMEN
Crude oil production (COP) is a high-pollution industry but the vast Amazon rainforest has been an active COP zone for South America. Although COP has been associated with a variety of health effects among workers around the world, such effects have not been adequately investigated in the Amazon region, especially at the community level. Therefore, this review was conducted to provide a report about COP in the Amazon of Ecuador and about its association with health status of indigenous human populations. Some epidemiological surveys in the Amazonian Territories indicate that COP has been associated with health problems in the surrounding populations, e.g. cancers in the stomach, rectum, skin, soft tissue, kidney and cervix in adults, and leukemia in children. In addition, some biomarkers and mechanistic studies show exposure effects. However, due to limitations from these studies, contradictory associations have been reported. Our review indicates that COP in the Amazonian territories of northern Ecuador was characterised by contamination which could have affected the indigenous and non-indigenous populations. However, there have not been dedicated investigations to provide relationships between the contamination and the subsequent exposure-health effects. Since indigenous populations have different lifestyle and cultures from regular city dwellers, systematic studies on their potential health hazards need to be conducted. Due to the remote locations and sparse populations, these new studies may involve the use of novel and genomic-based biomarkers as well as using high technology in the remote regions.
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Petróleo , Ecuador , Exposición a Riesgos Ambientales , Humanos , Salud PúblicaRESUMEN
Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB's with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ΔEij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ΔEij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental ¹H-NMR chemical shifts for the IMHB, with R² values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R².
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Enlace de Hidrógeno , Hidroquinonas/química , Espectroscopía de Resonancia Magnética , Polifenoles/químicaRESUMEN
The structure of the carbohydrate moiety of a natural phenolic glycoside can have a significant effect on the molecular interactions and physicochemical and pharmacokinetic properties of the entire compound, which may include anti-inflammatory and anticancer activities. The enzyme 6-O-α-rhamnosyl-ß-glucosidase (EC 3.2.1.168) has the capacity to transfer the rutinosyl moiety (6-O-α-l-rhamnopyranosyl-ß-d-glucopyranose) from 7-O-rutinosylated flavonoids to hydroxylated organic compounds. This transglycosylation reaction was optimized using hydroquinone (HQ) and hesperidin as rutinose acceptor and donor, respectively. Since HQ undergoes oxidation in a neutral to alkaline aqueous environment, the transglycosylation process was carried out at pH values ≤6.0. The structure of 4-hydroxyphenyl-ß-rutinoside was confirmed by NMR, that is, a single glycosylated product with a free hydroxyl group was formed. The highest yield of 4-hydroxyphenyl-ß-rutinoside (38%, regarding hesperidin) was achieved in a 2-h process at pH 5.0 and 30 °C, with 36 mM OH-acceptor and 5% (v/v) cosolvent. Under the same conditions, the enzyme synthesized glycoconjugates of various phenolic compounds (phloroglucinol, resorcinol, pyrogallol, catechol), with yields between 12% and 28% and an apparent direct linear relationship between the yield and the pKa value of the aglycon. This work is a contribution to the development of convenient and sustainable processes for the glycosylation of small phenolic compounds.
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Acremonium/enzimología , Disacáridos/química , Proteínas Fúngicas/química , Glicósido Hidrolasas/química , Acremonium/genética , Disacáridos/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Glicosilación , Concentración de Iones de HidrógenoRESUMEN
A fumaça do cigarro apresenta mais de 8700 substâncias identificadas, as quais já foram relacionadas com o desenvolvimento das mais variadas doenças. Dentre elas, uma substância relevante neste contexto de toxicidade do cigarro é a hidroquinona (HQ), gerada após a biotransformação do benzeno inalado. A HQ apresenta atividades relacionadas com a imunossupressão das respostas imune inata e adaptativa, observados mais no contexto in vitro e parcamente no in vivo; contudo, nenhum estudo ainda trouxe a abordagem do efeito da exposição à HQ sobre a resposta induzida por vacinação. Sendo assim, será que a exposição à fumaça do cigarro ou à HQ influenciaria na resposta de células B e geração de anticorpos induzidas por imunizações com vacinas anti-virais? Observamos que, após a exposição diária com 2500 ppm de HQ (equivalente a um maço de cigarro fumado / dia) por 8 semanas e vacinação com proteína recombinante codificadora do domínio III do Envelope do vírus da Dengue sorotipo 2 (EDIII) mais o adjuvante Alum, houve uma "tendência" para menores títulos de IgG total e IgG1 específicos à EDIII em camundongos C57BL/6. Análises histológicas revelaram um menor número de folículos e redução significativa de suas áreas no baço do grupo HQ em comparação com os não expostos. Para entendermos o efeito da HQ sobre a resposta humoral, realizamos uma análise de dados públicos de transcriptoma obtidas de amostras de sangue de humanos. Curiosamente, observamos que a HQ regula positivamente genes relacionados com a ativação de células B, assim como a migração e quimiotaxia de neutrófilos e outros leucócitos. Como é sabido que existe uma população de neutrófilos (N2) com a capacidade de auxiliar as respostas de células B, hipotetizamos que essas células poderiam disparar um mecanismo imunocompensatório que aumenta os títulos de anticorpos no grupo HQ
The cigarette smoke has more than 8700 harmful substances related to the occurrence of the most varied diseases. Among them, a relevant substance is the hydroquinone (HQ), generated upon the biotransformation of inhaled benzene. In vitro and in vivo analyses have demonstrated that HQ can suppress both innate and adaptive immune responses. However, no study has approached the effect of the HQ exposure on the vaccination-induced response. Thus, would the exposure to the cigarette smoke or HQ influence the B-cell and antibody responses elicited by immunizations with antiviral vaccines? We observed a "tendency" to lower titers of IgG total and IgG1 anti-EDIII in mice daily exposed to 2,500 ppm of HQ for 8 weeks and vaccinated. Histological analyses revealed a smaller number of follicles and a significant reduction in their area in the HQ group in comparison to their counterparts. In order to understand the effect of the HQ on the humoral response, we performed an analysis of public transcriptome data derived from human blood samples. We observed that the HQ up-regulates the expression of genes related to B cell activation as well as the migration and chemotaxis of neutrophils and other leukocytes. Considering that N2 neutrophils have the ability to help the B cell response, we have hypothesized that the HQ exposure may trigger an immunocompensatory effect, increasing the humoral response
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Animales , Masculino , Ratones , Vacunas/farmacología , Dengue , Hidroquinonas/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Immunospot Ligado a Enzimas/métodos , Transcriptoma/genética , Productos de Tabaco/efectos adversosRESUMEN
Calafate is a berry with high concentration of anthocyanins and hydroxycinnamic acids that grows in South Patagonia. To date, no metabolism studies of phenolic compounds using calafate have been carried out. A calafate extract was characterized by HPLC-DAD-ESI-MS/MS. After extract administration (300â¯mg/kg), a pharmacokinetic study of phenolic compounds in gerbil plasma was performed by GC-MS/MS. Sixteen phenolic acids increased after intake. Phenylacetic acid derivatives exhibit the highest concentration, while main increase of phenolic catabolites was observed 2â¯h post-intake. 3-hydroxyphenylacetic and phenylacetic acids increased at 4-8â¯h post-intake. All catabolites found in gerbil plasma exhibit concentration peaks between 0.1 and 1⯵M, however no parental anthocyanins were detected. Establish in vivo plasmatic concentration ranges of phenolic compounds derived from polyphenol consumption following WHO recommendations, plays a key role to carry out future in vitro assays in order to correctly assign biological benefits of calafate berry consumption.
Asunto(s)
Berberis/química , Gerbillinae/metabolismo , Fenoles/farmacocinética , Animales , Frutas , Gerbillinae/sangre , Peso Molecular , Espectrometría de Masas en TándemRESUMEN
A hidroquinona é usada como agente clareador há mais de 50 anos, e, nos últimos 20, suas segurança e toxicidade têm sido questionadas. Nesta revisão bibliográfica, pode-se verificar que seu potencial carcinogênico e mutagênico não foi comprovado até hoje em humanos. Além disso, estamos muito mais expostos à hidroquinona do que imaginamos, tanto em compostos cosméticos (por exemplo, tinturas de cabelos) quanto em alimentos, como a pera, bebidas e o café. Portanto, sua prescrição como despigmentante em concentrações de até 4% é segura e sem consequências sistêmicas.
Hydroquinone has been used as a whitening agent for more than 50 years, however its safety and toxicity have been questioned in the last two decades. In the present literature review, it is possible to verify that its carcinogenic and mutagenic potential in humans has not been proven to date. In addition, the population is in fact much more exposed to hydroquinone than commonly perceived, via both cosmetic compounds (e.g. hair dyes) and foods (e.g. pear, beverages and coffee). Therefore, prescribing hydroquinone as a depigmenting agent in concentrations of up to 4% is safe and devoid of systemic consequences.
RESUMEN
A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules.
Asunto(s)
Hidroquinonas/química , Modelos Moleculares , Conformación Molecular , Enlace de Hidrógeno , Hidroquinonas/síntesis química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
The degradation of paracetamol (PCT) and ciprofloxacin (CIP) was compared in relation to the generation of dihydroxylated products, Fe(III) reduction and reaction rate in the presence of dihydroxybenzene (DHB) compounds, or under irradiation with free iron (Fe3+) or citrate complex (Fecit) in Fenton or photo-Fenton process. The formation of hydroquinone (HQ) was observed only during PCT degradation in the dark, which increased drastically the rate of PCT degradation, since HQ formed was able to reduce Fe3+ and contributed to PCT degradation efficiency. When HQ was initially added, PCT and CIP degradation rate in the dark was much higher in comparison to the absence of HQ, due to the higher and faster formation of Fe2+ at the beginning of reaction. In the absence of HQ, no CIP degradation was observed; however, when HQ was added after 30 min, the degradation rate increased drastically. Ten PCT hydroxylated intermediates were identified in the absence of HQ, which could contribute for Fe(III) reduction and consequently to the degradation in a similar way as HQ. During CIP degradation, only one product of hydroxyl radical attack on benzene ring and substitution of the fluorine atom was identified when HQ was added to the reaction medium.
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Acetaminofén , Derivados del Benceno/química , Ciprofloxacina , Hierro/química , Contaminantes del Agua , Acetaminofén/análisis , Acetaminofén/química , Ciprofloxacina/análisis , Ciprofloxacina/química , Contaminantes del Agua/análisis , Contaminantes del Agua/química , Purificación del AguaRESUMEN
In this microcosm study, we analyzed the effect produced by hydroquinone on the expression of soil biological denitrification, in relation to the redox state of the soil, both in terms of intensity factor (Eh') and capacity factor (amount of oxidized or reduced compounds). The supplementation of an Argiudoll soil with hydroquinone decreased the soil apparent reduction potential (Eh') and soil dehydrogenase activity (formazan production from tetrazolium chloride reduction; redox capacity factor), the relationship between both factors being highly significative, r=0.99 (p<0.001). The bacterial population (measured by colony forming units) increased, and the production of N2O was greater (p<0.001) at 200 and 400µg/g dry soil doses. Furthermore, there was an inverse relationship between soil dehydrogenase activity and the number of bacteria (r=-0.82; p<0.05), increased denitrification activity and changes in the CO2/N2O ratio value. These results suggest that hydroquinone at supplemented doses modified the soil redox state and the functional structure of the microbial population. Acetate supplementation on soil with hydroquinone, to ensure the availability of an energy source for microbial development, confirmed the tendency of the results obtained with the supplementation of hydroquinone alone. The differences observed at increased doses of hydroquinone might be explained by differences on the hydroquinone redox species between treatments.