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51.
52.
N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity
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Ana Guardia Dr. Gulcin Gulten Dr. Raquel Fernandez Jesus Gómez Dr. Feng Wang Dr. Maire Convery Delia Blanco María Martínez Dr. Esther Pérez‐Herrán Marta Alonso Dr. Fátima Ortega Dr. Joaquín Rullás Dr. David Calvo Lydia Mata Dr. Robert Young Prof. James C. Sacchettini Dr. Alfonso Mendoza‐Losana Dr. Modesto Remuiñán Dr. Lluís Ballell Pages Dr. Julia Castro‐Pichel 《ChemMedChem》2016,11(7):687-701
Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis. 相似文献
53.
María ngeles Peinado David Ovelleiro María Luisa del Moral Raquel Hernndez Esther Martínez-Lara Eva Siles Jos Rafael Pedrajas María Luisa García-Martín Carlos Caro Sebastin Peralta María Encarnacin Morales María Adolfina Ruiz Santos Blanco 《International journal of molecular sciences》2022,23(1)
Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies. 相似文献
54.
Lucía Sánchez-Rodríguez Marina Kranjac Zvonimir Marijanović Igor Jerković David Pérez-López Ángel A. Carbonell-Barrachina Francisca Hernández Esther Sendra 《Journal of the American Oil Chemists' Society》2020,97(5):449-462
Three new regulated deficit irrigation (RDI) treatments were applied to “Arbequina” olive orchards during pit hardening. Oil quality was determined by measuring analytical parameters for olive oil grading, antioxidant activity, total phenol content, fatty acid profile, volatile compounds profile, and sensory analysis. Oils from RDI were classified as “extra virgin olive oil” and their quality was improved due to their higher antioxidant potential (ABTS+ [increased ~75%] and DPPH˙ [increased ~25%] assays) and phenols (increased ~53%) than control. Concentration of total volatile compounds decreased (~27%) but RDI olive oils showed a more balanced profile (alcohols, aldehydes, and esters). Monounsaturated fatty acid content increased (~5%) and atherogenic and thrombogenic indexes decreased (~8.5%) in RDI olive oil. Regarding sensory analysis, RDI provided more balanced oils with higher fruit aroma than control. Other benefits of RDI olive oil, when compared with oil from full irrigated orchards are reduced use of water and improved functional and sensory quality. 相似文献
55.
Gilbert Rodríguez Eudes Villanueva Danco Cortez Esther Sanchez Elza Aguirre Alyssa Hidalgo 《Journal of the American Oil Chemists' Society》2020,97(7):729-735
Chia and sesame oils are important sources of essential fatty acids; however, their ω-3:ω-6 proportions do not comply with nutritional recommendation. A feasible approach to improve the ratio is to blend different oils, but only after understanding physical and chemical changes of the new matrix. Objective of the investigation was to determine the physico-chemical characteristics and the oxidative stability index (OSI), using the Rancimat method, of chia-sesame oil blends. The four ω-3:ω-6 blends tested (1:4, 1:6, 1:8, and 1:10) were exposed to temperatures of 110, 120, and 130 °C. The OSI values of the mixtures varied between 6.24–8.08, 3.07–4.00, and 1.62–2.01 hours for each temperature, respectively. In addition, their mean activation energy, enthalpy, entropy, and Q10 were 88.4 kJ/mol, 85.2 kJ/mol, −41.1 J/mol K, and 2.0. Finally, a shelf life prediction performed at 25 °C indicated stability times between 80 and 123 days. Therefore, combining chia and sesame oils produced blends with a good balance of essential fatty acids. 相似文献
56.
Gustavo D. Campagnaro Hamza A. A. Elati Sofia Balaska Maria Esther Martin Abril Manal J. Natto Fabian Hulpia Kelly Lee Lilach Sheiner Serge Van Calenbergh Harry P. de Koning 《International journal of molecular sciences》2022,23(2)
Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (Km ~1 µM), while inosine and guanosine displayed Ki values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases. 相似文献
57.
Hoelzer K Sauders BD Sanchez MD Olsen PT Pickett MM Mangione KJ Rice DH Corby J Stich S Fortes ED Roof SE Grohn YT Wiedmann M Oliver HF 《Journal of food protection》2011,74(7):1083-1095
Despite growing concerns about cross-contamination of ready-to-eat foods with Listeria monocytogenes, our knowledge about the ecology and transmission of L. monocytogenes in retail establishments has remained limited. We conducted a cross-sectional study to characterize the prevalence, distribution, and subtype diversity of L. monocytogenes in 120 New York State retail deli establishments that were hypothesized to present an increased risk for environmental L. monocytogenes contamination (i.e., small establishments and establishments with a history of failed New York State Agriculture and Markets inspections). Analysis of these data along with previously reported data for 121 predominantly larger retail establishments in New York State identified establishment size, geographic location, and inspection history as significant predictors of L. monocytogenes presence and prevalence. The odds of an establishment being L. monocytogenes positive were approximately twice as high for large establishments, establishments located in New York City, or establishments with poor inspection history (as compared with establishments without these attributes), even though correlation between location and inspection history complicated interpretation of results. Within an establishment, L. monocytogenes was significantly more prevalent on nonfood contact surfaces than on food contact surfaces; prevalence was particularly high for floors and in floor drains, sinks, the dairy case, and milk crates. L. monocytogenes subtype diversity differed between sites, with lineage I isolates significantly associated with nonfood contact surfaces and lineage II isolates significantly associated with food contact surfaces. Isolates belonging to the same ribotype were often found dispersed across multiple sites within an operation. 相似文献
58.
Protective effect of a pomace olive oil concentrated in triterpenic acids in alterations related to hypertension in rats: Mechanisms involved
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59.
Laser‐induced surface structures on gold‐coated polymers: Influence of morphology on surface‐enhanced Raman scattering enhancement
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Esther Rebollar Margarita Hernández Mikel Sanz Susana Pérez Tiberio A. Ezquerra Marta Castillejo 《应用聚合物科学杂志》2015,132(45)
The fabrication of highly sensitive and reproducible substrates for Surface‐Enhanced Raman Scattering (SERS) remains a challenging scientific and technological issue. In this work, laser‐induced periodic surface structures are generated on poly(trimethylen terephthalate) films upon laser irradiation with the linearly polarized beams of a Nd:YAG laser (4th harmonic, 266 nm), an ArF excimer laser (193 nm), and a Titanium:sapphire laser (795 nm), resulting in periods close to the laser wavelength when irradiating at normal incidence, and larger periods for different angles of incidence. Additional irradiation with a circularly polarized beam at 266 nm produces superficial circular structures. The nanostructured polymers are coated with a nanoparticle assembled gold layer by pulsed laser deposition at 213 nm. The capabilities of these substrates for SERS are evaluated using benzenethiol as a test molecule and different degrees of Raman signal enhancement are observed depending on the nanostructure type. The highest enhancement factor is obtained by for nanostructured substrates with the highest values of period, depth, and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42770. 相似文献
60.
Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner
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Ngoc‐Anh Le Margaret R. Diffenderfer Nuntakorn Thongtang Esther M. M. Ooi P. Hugh R. Barrett Katalin V. Horvath Gregory G. Dolnikowski Bela F. Asztalos Ernst J. Schaefer W. Virgil Brown 《Lipids》2015,50(5):447-458
Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics. 相似文献