RESUMEN

Aim: This study aimed to enhance the aqueous dissolution of SRPK inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340).Materials & Methods: A complex with p-sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via 1H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines.Results & conclusion: The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by 1H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.

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Asunto(s)

Antineoplásicos , Calixarenos , Supervivencia Celular , Calixarenos/química , Calixarenos/farmacología , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Supervivencia Celular/efectos de los fármacos , Fenoles/química , Fenoles/farmacología , Ratones , Espectroscopía de Resonancia Magnética , Animales , Ácidos Sulfónicos/química , Ácidos Sulfónicos/antagonistas & inhibidores , Ácidos Sulfónicos/farmacología , Línea Celular Tumoral , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Proliferación Celular/efectos de los fármacos , Piperidinas/química , Piperidinas/farmacología

RESUMEN

We present our results on the synthesis and preliminary in silico and in vitro studies of the toxicology and antioxidant properties of selenylated analogs of Tacrine. Initially, we synthesized 2-aminobenzonitriles containing an organic selenium moiety, resulting in sixteen compounds with various substituents linked to the portion derived from diorganyl diselenide. These compounds were then used as substrates in reactions with cyclic ketones, in the presence of 1.4 equivalents of trifluoroboroetherate as a Lewis acid, to synthesize selenylated analogs of Tacrine with yields ranging from 20 % to 87 %. In silico studies explored computational parameters related to antioxidant activity and hepatotoxicity. In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated.

Asunto(s)

Antioxidantes , Compuestos de Bifenilo , Picratos , Tacrina , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Tacrina/química , Tacrina/farmacología , Tacrina/síntesis química , Animales , Picratos/antagonistas & inhibidores , Picratos/química , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Estructura Molecular , Ratas , Masculino , Benzotiazoles/química , Benzotiazoles/síntesis química , Simulación por Computador , Ácidos Sulfónicos/química , Ácidos Sulfónicos/antagonistas & inhibidores , Compuestos de Organoselenio/química , Compuestos de Organoselenio/farmacología , Compuestos de Organoselenio/síntesis química , Compuestos de Organoselenio/toxicidad

RESUMEN

Chicken meat production has increased over the years, leading to a proportional increase in waste generation, which often contains high levels of proteins, such as viscera. Therefore, this study aimed to investigate the enzymatic hydrolysis of chicken viscera proteins as a strategy to value solid waste from the poultry industry. The hydrolysates were characterized for their antioxidant properties and molecular weight distribution. Additionally, the enzymatic hydrolysis process was scaled up from 125 mL flasks with 50 mL of protein solution to 3 L using a 6 L bioreactor. The enzymatic hydrolysis of chicken viscera proteins using a binary mixture of proteases (85.25 U/mL of each enzyme, Alcalase and Flavourzyme, totaling 170.5 U/mL) resulted in an increase of up to 245% in 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, 353% 2,2-diphenyl-1-picryl-hydrazyl (DPPH) in radical scavenging, 69% in Ferric Reducing Antioxidant Power Assay (FRAP) and 146% in total reducing capacity (TRC). The antioxidant properties of the protein hydrolysates are preserved during the scale-up of enzymatic hydrolysis. Protein fractions smaller than 5 kDa showed the highest ABTS and DPPH radical scavenging activities, while fractions greater than 30 kDa showed the best results for the FRAP method.

Asunto(s)

Antioxidantes , Pollos , Hidrolisados de Proteína , Animales , Antioxidantes/farmacología , Antioxidantes/química , Hidrólisis , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/metabolismo , Vísceras/metabolismo , Vísceras/química , Compuestos de Bifenilo/química , Subtilisinas/metabolismo , Subtilisinas/química , Picratos/química , Ácidos Sulfónicos/química , Benzotiazoles/química , Reactores Biológicos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Endopeptidasas/metabolismo

RESUMEN

The infection of mammalian cells by enveloped viruses is triggered by the interaction of viral envelope glycoproteins with the glycosaminoglycan, heparan sulfate. By mimicking this carbohydrate, some anionic polysaccharides can block this interaction and inhibit viral entry and infection. As heparan sulfate carries both carboxyl and sulfate groups, this work focused on the derivatization of a (1→3)(1→6)-ß-D-glucan, botryosphaeran, with these negatively-charged groups in an attempt to improve its antiviral activity. Carboxyl and sulfonate groups were introduced by carboxymethylation and sulfonylation reactions, respectively. Three derivatives with the same degree of carboxymethylation (0.9) and different degrees of sulfonation (0.1; 0.2; 0.4) were obtained. All derivatives were chemically characterized and evaluated for their antiviral activity against herpes (HSV-1, strains KOS and AR) and dengue (DENV-2) viruses. Carboxymethylated botryosphaeran did not inhibit the viruses, while all sulfonated-carboxymethylated derivatives were able to inhibit HSV-1. DENV-2 was inhibited only by one of these derivatives with an intermediate degree of sulfonation (0.2), demonstrating that the dengue virus is more resistant to anionic ß-D-glucans than the Herpes simplex virus. By comparison with a previous study on the antiviral activity of sulfonated botryosphaerans, we conclude that the presence of carboxymethyl groups might have a detrimental effect on antiviral activity.

Asunto(s)

Antivirales/farmacología , Virus del Dengue/efectos de los fármacos , Herpesviridae/efectos de los fármacos , Ácidos Sulfónicos/química , beta-Glucanos/química , Animales , Antivirales/química , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Virus del Dengue/fisiología , Glucanos/química , Glucanos/farmacología , Herpesviridae/fisiología , Metilación , Células Vero , Internalización del Virus/efectos de los fármacos , beta-Glucanos/farmacología

RESUMEN

Graphene is a two-dimensional semiconducting material whose application for diagnostics has been a real game-changer in terms of sensitivity and response time, variables of paramount importance to stop the COVID-19 spreading. Nevertheless, strategies for the modification of docking recognition and antifouling elements to obtain covalent-like stability without the disruption of the graphene band structure are still needed. In this work, we conducted surface engineering of graphene through heterofunctional supramolecular-covalent scaffolds based on vinylsulfonated-polyamines (PA-VS). In these scaffolds, one side binds graphene through multivalent π-π interactions with pyrene groups, and the other side presents vinylsulfonated pending groups that can be used for covalent binding. The construction of PA-VS scaffolds was demonstrated by spectroscopic ellipsometry, Raman spectroscopy, and contact angle measurements. The covalent binding of -SH, -NH2, or -OH groups was confirmed, and it evidenced great chemical versatility. After field-effect studies, we found that the PA-VS-based scaffolds do not disrupt the semiconducting properties of graphene. Moreover, the scaffolds were covalently modified with poly(ethylene glycol) (PEG), which improved the resistance to nonspecific proteins by almost 7-fold compared to the widely used PEG-monopyrene approach. The attachment of recognition elements to PA-VS was optimized for concanavalin A (ConA), a model lectin with a high affinity to glycans. Lastly, the platform was implemented for the rapid, sensitive, and regenerable recognition of SARS-CoV-2 spike protein and human ferritin in lab-made samples. Those two are the target molecules of major importance for the rapid detection and monitoring of COVID-19-positive patients. For that purpose, monoclonal antibodies (mAbs) were bound to the scaffolds, resulting in a surface coverage of 436 ± 30 ng/cm2. KD affinity constants of 48.4 and 2.54 nM were obtained by surface plasmon resonance (SPR) spectroscopy for SARS-CoV-2 spike protein and human ferritin binding on these supramolecular scaffolds, respectively.

Asunto(s)

Biomarcadores/análisis , COVID-19/diagnóstico , Grafito/química , Inmunoensayo/métodos , Glicoproteína de la Espiga del Coronavirus/análisis , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Etilenos/química , Ferritinas/inmunología , Ferritinas/metabolismo , Humanos , Sistemas de Atención de Punto , Poliaminas/química , Polietilenglicoles/química , Pirenos/química , Teoría Cuántica , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/metabolismo , Semiconductores , Glicoproteína de la Espiga del Coronavirus/inmunología , Ácidos Sulfónicos/química , Resonancia por Plasmón de Superficie

RESUMEN

There is a growing environmental concern in the world for replacing the traditional petroleum-based products. The aim of this work was to evaluate the structure - property relationship of banana peel lignins (BPLs) as antioxidant and antimicrobial agents by controlling the parameters of organosolv process. The milled banana peel was hydrolyzed using an aqueous acetic acid solution (70, 80 and 90% v/v) and 2.0% v/v HCl at 110 °C for 1, 2 and 3 h. BPLs were characterized by FTIR, 1H NMR, 1H13C HSQC, 31P NMR, GPC and TGA. The antioxidant capacity of BPLs was evaluated by DPPH, ABTS and H2O2 assays, comparing their performance with that of ascorbic and gallic acid. The antimicrobial activity of BPLs was evaluated against E. coli. The reaction time and acetic acid/water ratio had significant effects on the yield and purity of BPLs. The composition of organosolv solution also affected their total amount of hydroxyls (0.71-0.82 mmol g-1), Mw (2759-3954 g mol-1), Tonset (232-254 °C), antioxidant and antimicrobial activities. It can be concluded that the control of organosolv parameters can be a useful tool for tuning the structural features of lignins and to maximize their performance.

Asunto(s)

Antiinfecciosos/farmacología , Antioxidantes/farmacología , Lignina/farmacología , Musa/química , Solventes/química , Temperatura , Bacterias/efectos de los fármacos , Benzotiazoles/química , Compuestos de Bifenilo/química , Hongos/efectos de los fármacos , Peróxido de Hidrógeno/química , Concentración 50 Inhibidora , Lignina/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Peso Molecular , Picratos/química , Soluciones , Espectroscopía Infrarroja por Transformada de Fourier , Ácidos Sulfónicos/química , Termogravimetría

RESUMEN

The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06-150 µg/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150 µg/mL) and CN67 (120 µg/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37 µg/mL) and turmeric powder (9.37 or 4.68 µg/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65-130.9 µM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.

Asunto(s)

Antiinfecciosos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Bioprospección , Candida albicans/efectos de los fármacos , Diarilheptanoides/farmacología , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/toxicidad , Antioxidantes/síntesis química , Antioxidantes/toxicidad , Bacterias/crecimiento & desarrollo , Benzotiazoles/química , Compuestos de Bifenilo/química , Coagulación Sanguínea/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Diarilheptanoides/síntesis química , Diarilheptanoides/toxicidad , Farmacorresistencia Microbiana , Hemólisis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/toxicidad , Picratos/química , Oveja Doméstica , Ácidos Sulfónicos/química

RESUMEN

The essential oil (EO), the methanolic (MeOH), and the 70% ethanolic (70% EtOH) extracts obtained from the aerial parts of Ocimum campechianum Mill. (Ecuador) were chemically characterized through gas-chromatography coupled to mass spectrometry detector (GC-MS), high-performance liquid chromatography coupled to diode array-mass spectrometry detectors (HPLC-DAD-MS) and studied for their in vitro biological activity. The radical scavenger activity, performed by spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, highlighted significant IC50 values for the EO, extracts and their main constituents (eugenol and rosmarinic acid). EO (and eugenol) showed noteworthy activity against Pseudomonas syringae pv. syringae and a moderate effect against clinical Candida strains, with possible synergism in association to fluconazole against the latter microorganisms. The extracts and pure molecules exhibited weak cytotoxic activity against the HaCat cell line and no mutagenicity against Salmonella typhimurium TA98 and TA100 strains, giving indication of safety. Instead, EO showed a weak activity against adenocarcinomic human alveolar basal epithelial cells (A549). The above-mentioned evidence leads us to suggest a potential use of the crude drug, extracts, and EO in cosmetic formulation and food supplements as antioxidant agents. In addition, EO may also have a possible application in plant protection and anti-Candida formulations.

Asunto(s)

Cinamatos/farmacología , Depsidos/farmacología , Eugenol/farmacología , Ocimum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células A549 , Antibacterianos/farmacología , Antioxidantes/farmacología , Benzotiazoles/química , Compuestos de Bifenilo/química , Candida/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Ecuador , Fluconazol/farmacología , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Mutagénesis , Aceites Volátiles/análisis , Picratos/química , Ácidos Sulfónicos/química , Ácido Rosmarínico

RESUMEN

Mangifera indica Linn popularly known as mango is used in folk medicine to treat gastrointestinal disorders. The aim of this study was to identify the metabolomic composition of lyophilized extract of mango leaf (MIE), to evaluate the antioxidant activity on several oxidative stress systems (DPPH, FRAP, TBARS, and ABTS), the spasmolytic and antispasmodic activity, and intestinal protective effect on oxidative stress induced by H2O2 in rat ileum. Twenty-nine metabolites were identified and characterized based on their ultra-high-performance liquid chromatography (UHPLC) high-resolution orbitrap mass spectrometry, these include: benzophenone derivatives, xanthones, phenolic acids, fatty acids, flavonoids and procyanidins. Extract demonstrated a high antioxidant activity in in-vitro assays. MIE relaxed (p < 0.001) intestinal segments of rat pre-contracted with acetylcholine (ACh) (10-5 M). Pre-incubation of intestinal segments with 100 µg/mL MIE significantly reduced (p < 0.001) the contraction to H2O2. Similar effects were observed with mangiferin and quercetin (10-5 M; p < 0.05) but not for gallic acid. Chronic treatment of rats with MIE (50 mg/kg) for 28 days significantly reduced (p < 0.001) the H2O2-induced contractions. MIE exhibited a strong antioxidant activity, spasmolytic and antispasmodic activity, which could contribute to its use as an alternative for the management of several intestinal diseases related to oxidative stress.

Asunto(s)

Antioxidantes/farmacología , Íleon/efectos de los fármacos , Mangifera/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Benzofenonas/química , Benzotiazoles/química , Compuestos de Bifenilo/química , Cromatografía Líquida de Alta Presión , Ácido Gálico/farmacología , Peróxido de Hidrógeno/química , Peroxidación de Lípido , Masculino , Metabolómica , Modelos Biológicos , Estrés Oxidativo , Parasimpatolíticos/farmacología , Fitoquímicos/farmacología , Picratos/química , Quercetina/farmacología , Ratas , Ácidos Sulfónicos/química , Sustancias Reactivas al Ácido Tiobarbitúrico/química , Xantonas/química

RESUMEN

UPLC-QTOF-MSE phenolic profile of kombuchas produced from the fermentation of green tea or black tea at 25 °C for 10 days was investigated along with the determination of their antioxidant capacities, antibacterial and antiproliferative activities. Overall, 127 phenolic compounds (70.2% flavonoids, 18.3% phenolic acids, 8.4% other polyphenols, 2.3% lignans and 0.8% stilbenes) were identified, with 103 phenolic compounds reported for the first time in kombuchas. A greater diversity and abundance of phenolic compounds was detected in black tea kombucha, which resulted in a higher antioxidant capacity. However, the green tea kombucha was the only one that presented antibacterial activity against all the bacteria tested and an increased antiproliferative activity against the cancer cell lines, which was attributed to the presence of catechins among the most abundant phenolic compounds and verbascoside as an exclusive compound. Thus, the type of tea used in the kombucha production interferes in its bioactive composition and properties.

Asunto(s)

Antibacterianos/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Té de Kombucha/análisis , Fenoles/química , Antineoplásicos/química , Bacterias/efectos de los fármacos , Benzotiazoles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad Microbiana , Ácidos Sulfónicos/química

RESUMEN

The present study demonstrated the preparation of three different acid-functionalised magnetic nanoparticles (MNPs) and evaluation for their catalytic efficacy in hydrolysis of cellobiose. Initially, iron oxide (Fe3O4)MNPs were synthesised, which further modified by applying silica coating (Fe3O4-MNPs@Si) and functionalised with alkylsulfonic acid (Fe3O4-MNPs@Si@AS), butylcarboxylic acid (Fe3O4-MNPs@Si@BCOOH) and sulphonic acid (Fe3O4-MNPs@Si@SO3H) groups. The Fourier transform infrared analysis confirmed the presence of above-mentioned acid functional groups on MNPs. Similarly, X-ray diffraction pattern and energy dispersive X-ray spectroscopy analysis confirmed the crystalline nature and elemental composition of MNPs, respectively. TEM micrographs showed the synthesis of spherical and polydispersed nanoparticles having diameter size in the range of 20-80 nm. Cellobiose hydrolysis was used as a model reaction to evaluate the catalytic efficacy of acid-functionalised nanoparticles. A maximum 74.8% cellobiose conversion was reported in case of Fe3O4-MNPs@Si@SO3H in first cycle of hydrolysis. Moreover, thus used acid-functionalised MNPs were magnetically separated and reused. In second cycle of hydrolysis, Fe3O4-MNPs@Si@SO3H showed 49.8% cellobiose conversion followed by Fe3O4-MNPs@Si@AS (45%) and Fe3O4-MNPs@Si@BCOOH (18.3%). However, similar pattern was reported in case of third cycle of hydrolysis. The proposed approach is considered as rapid and convenient. Moreover, reuse of acid-functionalised MNPs makes the process economically viable.

Asunto(s)

Celobiosa/química , Nanopartículas de Magnetita/química , Ácidos Sulfónicos/química , Ácidos Carboxílicos/química , Celobiosa/análisis , Hidrólisis , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS•+) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p-coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves' extracts of A. linaria showed a high scavenging activity of DPPH• and ABTS•+ radicals (IC50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds.

Asunto(s)

Antioxidantes/química , Asclepias/química , Proliferación Celular/efectos de los fármacos , Fenoles/química , Antioxidantes/farmacología , Ácido Ascórbico/química , Benzotiazoles/química , Compuestos de Bifenilo/química , Cromatografía Liquida , Depuradores de Radicales Libres/química , Humanos , Células K562 , Metanol/química , Fenoles/clasificación , Fenoles/farmacología , Picratos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Quercetina/química , Ácidos Sulfónicos/química , Espectrometría de Masas en Tándem

RESUMEN

Resorcinarenes are macrocyclic molecules that can bind different molecules in a supramolecular fashion. There are some sulfonated water-soluble derivatives that have been investigated to bind proteins avoiding fibrillation. The interaction with enzymes such as catalase (CAT) allows the interpretation of the possible effects of the use of resorcinarenes on human health or environmental applications. The interaction of five sulfonated resorcinarenes with different chemical structures was investigated by using different biophysical methods. The results of the spectroscopic experiments (fluorescence, synchronous fluorescence, and Uv-vis spectrophotometry) show different degrees of structural change, indicating that the binding of the macrocycles that were studied causes alterations on the conformation of CAT. The resorcinarenes reduce the activity of CAT in different extent, two macrocycles (named Na4EtRA and Na4PrRA, according to ethyl or propyl moieties at the lower pendant group) exhibit significant inhibition capacity (until ca. 70%). The study about inhibition types reveals a non-competitive mechanism for all the studied resorcinarenes. The docking calculations reveal that the macrocycles bond mainly to two domains of the CAT structure, which are not related with the active site.

Asunto(s)

Calixarenos/química , Calixarenos/metabolismo , Catalasa/metabolismo , Hígado/enzimología , Fenilalanina/análogos & derivados , Ácidos Sulfónicos/química , Agua/química , Animales , Calixarenos/farmacología , Catalasa/química , Bovinos , Simulación del Acoplamiento Molecular , Fenilalanina/química , Fenilalanina/metabolismo , Fenilalanina/farmacología , Unión Proteica , Conformación Proteica , Solubilidad

RESUMEN

Sulfated polysaccharides are known to display activity against enveloped viruses, such as herpes and dengue. The aim of this work was to assess the antiviral activity of botryosphaeran, a fungal exocellular (1 → 3)(1 → 6)-ß-d-glucan devoid of sulfate groups, and its chemically sulfonated derivatives, against herpes simplex virus (HSV), dengue virus (DENV) and poliovirus (PV). The natural parent polysaccharide inhibited acyclovir-sensitive HSV (HSV-KOS) infection in Vero cells (IC50 of 39.3 µg mL-1), while the IC50 against acyclovir-resistant HSV (HSV-AR) was 47.5 µg mL-1. Botryosphaeran was derivatized by sulfonylation with chlorosulfonic acid to prepare two sulfonated derivatives, S1 and S2, with degrees of substitution (DS) of 0.4 and 1.1, respectively. Antiviral evaluation of S1 and S2 gave the IC50 of 3.0 and 2.4 µg mL-1 against HSV-KOS, and 7.3 and 2.7 µg mL-1 against HSV-AR, respectively. This study demonstrated for the first time that native botryosphaeran inhibited HSV infection, albeit moderately, while its sulfonated derivatives developed high activity against viral infection. DENV inhibition was weak for botryosphaeran, but remarkably stronger for S1 and S2. All compounds were inactive against PV, as it lacked a viral envelope. The presence of sulfate groups and the DS were confirmed to be important features for antiviral activity.

Asunto(s)

Antivirales/química , Antivirales/farmacología , Virus del Dengue/efectos de los fármacos , Glucanos/química , Glucanos/farmacología , Simplexvirus/efectos de los fármacos , Ácidos Sulfónicos/química , Animales , Chlorocebus aethiops , Poliovirus/efectos de los fármacos , Células Vero

RESUMEN

To date, a large number of active molecules are hydrophilic and aromatic low molecular-weight drugs (HALMD). Unfortunately, the low capacity of these molecules to interact with excipients and the fast release when a formulation containing them is exposed to biological media jeopardize the elaboration of drug delivery systems by using noncovalent interactions. In this work, a new, green, and highly efficient methodology to noncovalently attach HALMD to hydrophilic aromatic polymers to create nanocarriers is presented. The proposed method is simple and consists in mixing an aqueous solution containing HALMD (model drugs: imipramine, amitriptyline, or cyclobenzaprine) with another aqueous solution containing the aromatic polymer [model polymer: poly(sodium 4-styrenesulfonate) (PSS)]. NMR experiments demonstrate strong chemical shifting of HALMD aromatic rings when interacting with PSS, evidencing aromatic-aromatic interactions. Ion pair formation and aggregation produce the collapse of the system in the form of nanoparticles. The obtained nanocarriers are spheroidal, their size ranging between 120 and 170 nm, and possess low polydispersity (≤0.2) and negative zeta potential (from -60 to -80 mV); conversely, the absence of the aromatic group in the polymer does not allow the formation of nanostructures. Importantly, in addition to high drug association efficiencies (≥90%), the formed nanocarriers show drug loading values never evidenced for other systems comprising HALMD, reaching ≈50%. Diafiltration and stopped flow experiments evidenced kinetic drug entrapment governed by molecular rearrangements. Importantly, the nanocarriers are stable in suspension for at least 18 days and are also stable when exposed to different high ionic strength, pH, and temperature values. Finally, they are transformable to a reconstitutable dry powder without losing their original characteristics. Considering the large quantity of HALMD with importance in therapeutics and the simplicity of the presented strategy, we envisage these results as the basis to elaborate a number of drug delivery systems with applications in different pathologies.

Asunto(s)

Antidepresivos Tricíclicos/química , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Polímeros/química , Ácidos Sulfónicos/química , Liberación de Fármacos , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Peso Molecular , Nanomedicina/métodos , Tamaño de la Partícula

RESUMEN

Ocotea minarum is a native plant from Brazil, popularly known as "canelinha" or "canela vassoura." The objective of this study was to investigate the chemical composition of the extracts of the bark and the leaves of O. minarum and to evaluate its antimicrobial and antioxidant activities. The phenolic compounds, flavonoids and tanins, were quantified with the reagents Folin-Ciocalteu, aluminium chloride, and vanillin. The chemical profile was performed by HPLC-DAD. The minimum inhibitory concentration was evaluated by the microdilution in a broth method. The antioxidant activity was measured by the capture of free radicals 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid). In addition, protection against oxidative hemolysis and generation of malondialdehyde were evaluated in human erythrocytes. The composition of the extracts included the caffeic acid, p-coumaric acid, and rosmarinic acid, besides the flavonoids quercetin and luteolin. The EEL showed bacteriostatic action of 1000 µg/mL for all evaluated Salmonella Typhimurium, Salmonella Enteritidis, Pseudomonas aeruginosa, and Proteus mirabilis, and the EHEB had a moderate antifungal action against Candida krusei and Cryptococcus gattii (250 µg/mL). IC50 values of 8.19 (EEL) and 4.51 µg/mL (EEB) in the assay with DPPH and 6.25 (EEL) and 2.87 µg/mL (EEB) in the assay with ABTS were obtained. Up to the 3rd hour of oxidative hemolysis testing induced by AAPH, the EEB and EEL had a protective action, reducing the malondialdehyde. In conclusion, the data indicate that the O. minarum extracts can be evaluated as bioactive supplies for the development of new drugs for the prevention and treatment of diseases related to oxidative stress and microbial infections.

Asunto(s)

Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Ocotea/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Benzotiazoles/química , Compuestos de Bifenilo/química , Candida/efectos de los fármacos , Cryptococcus gattii/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Picratos/química , Proteus mirabilis/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Salmonella enteritidis/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Ácidos Sulfónicos/química

RESUMEN

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 µg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 µg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 µg/mL (TNF-α) and 58.12 µg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1ß (36%) was recorded at 200 µg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Diterpenos/farmacología , Diuréticos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/toxicidad , Antioxidantes/química , Antioxidantes/uso terapéutico , Antioxidantes/toxicidad , Asteraceae , Benzotiazoles/química , Compuestos de Bifenilo/química , Carragenina , Ensayo Cometa , Citocinas/metabolismo , Diterpenos/química , Diterpenos/uso terapéutico , Diterpenos/toxicidad , Diuréticos/química , Diuréticos/uso terapéutico , Diuréticos/toxicidad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Picratos/química , Ácidos Sulfónicos/química

RESUMEN

Juçara fruit (Euterpe edulis) has received attention due to its similarities to Euterpe oleracea (Açaí). The aim of this study was to evaluate the cytotoxicity, bioactive compounds, antioxidant capacities and chemopreventive activities of the fruit pulps of six populations of E. edulis (J1-J6) and one population of E. espiritosantense from different ecological regions. ESI(-)-FT-ICR-MS was used to evaluate the pulp composition. The varieties J1 and J4 presented higher polyphenol contents, while J2 and J5 showed higher anthocyanin contents. ESI-FT-ICR MS identified cyanidin-3-rutinoside (J1, J2, J3, J4, J5, J7), protocatechuic acid, methylhydroxybenzoate hexoside and rutin (J1 to J7) and malvidin-glicoside (J2 to J5). The J2, J3, J4, J5 and J6 samples inhibited inducible nitric oxide synthase (iNOS). The chemoprevention biomarker quinone reductase was significantly induced by J6. Pulp from plants J3, J4, J6 and J7 significantly reduced the inflammatory cytokine TNF-α, and J6 was selected as having the most potential for cultivation and consumption.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Euterpe/química , Frutas/química , Fitoquímicos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Benzotiazoles/química , Línea Celular Tumoral , Citocinas/metabolismo , Euterpe/genética , Frutas/genética , Genotipo , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fitoquímicos/aislamiento & purificación , Células RAW 264.7 , Ácidos Sulfónicos/química

RESUMEN

Persea americana (avocado) is a fruit consumed worldwide; however, since avocado leaves are apparently a natural ingredient that can be used as a traditional medicine, they can be a potential source of bioactive compounds. This study aimed to analyze the antioxidant activity of seven Mexican avocado leaf extracts by DPPH•, ABTS•+, and lipid peroxidation (LPO), and to identify the compound profile by liquid chromatography coupled to mass spectrometry/electron spray ionization. The highest free radical-scavenging activity was observed for Platano Delgado and Criollo 6 avocado cultivars havin IC50 values of 271.86 ± 13.69 and 269.56 ± 6.53 for DPPH• and ABTS•+ radicals, respectively, while the best result for lipid oxidation inhibition was registered in Criollo 6 cultivar extract. In this study forty-one compounds were detected in avocado leaves of the the seven cultivars analyzed, and of these compounds, eighteen phenolics were identified for first time in such plant material. The present study demonstrated that Mexican cultivars of Persea americana possess diverse polyphenolic compounds with strong antioxidant activity, which might be useful in the food and pharmaceutical industries.

Asunto(s)

Antioxidantes/química , Persea/química , Extractos Vegetales/química , Polifenoles/química , Benzotiazoles/química , Compuestos de Bifenilo/química , Depuradores de Radicales Libres/química , Peroxidación de Lípido/efectos de los fármacos , Picratos/química , Hojas de la Planta/química , Ácidos Sulfónicos/química

RESUMEN

Due to the high sensitivity to alterations in microenvironment polarity of macromolecules, pyrene and its derivatives have long been applied in biosciences. Human serum albumin (HSA), besides its numerous physiological functions, is the main responsible by transport of endogenous and exogenous compounds in the circulatory system. Here, a comprehensive study was carry out to understand the interaction between HSA and the pyrene derivative 1-pyrenesulfonic acid (PMS), which showed a singular behaviour when bound to this protein. The complexation of PMS with HSA was studied by steady state, time-resolved and anisotropy fluorescence, induction of circular dichroism (ICD) and molecular docking. The fluorescence quenching of PMS by HSA was abnormal, being stronger at lower concentration of the quencher. Similar behaviour was obtained by measuring the ICD signal and fluorescence lifetime of PMS complexed in HSA. The displacement of PMS by site-specific drugs showed that this probe occupied both sites, but with higher affinity for site II. The movement of PMS between these main binding sites was responsible by the abnormal effect. Using the holo (PDB: ID 1A06) and apo (PDB: ID 1E7A) HSA structures, the experimental results were corroborated by molecular docking simulation. The abnormal spectroscopic behaviour of PMS is related to its binding in different regions in the protein. The movement of PMS into the protein can be traced by alteration in the spectroscopic signals. These findings bring a new point of view about the use of fluorescence quenching to characterize the interaction between albumin and ligands.

Asunto(s)

Conalbúmina/metabolismo , Pirenos/metabolismo , Albúmina Sérica Bovina/metabolismo , Albúmina Sérica Humana/metabolismo , Ácidos Sulfónicos/metabolismo , Animales , Anisotropía , Sitios de Unión , Bovinos , Dicroismo Circular , Fluorescencia , Humanos , Simulación del Acoplamiento Molecular , Pirenos/química , Ácidos Sulfónicos/química , Termodinámica , Factores de Tiempo , Triptófano/análogos & derivados , Triptófano/química