Substitutions of fluorine atoms and phenoxy groups in the synthesis of quinoxaline 1,4-di-N-oxide derivatives.

The unexpected substitution of fluorine atoms and phenoxy groups attached to quinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl- and 2-phenoxy- 3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction. The tendency of fluorine atoms linked to quinoxaline or benzofuroxan rings to be replaced by a methoxy group when dissolved in an ammonia saturated solution of methanol was clearly demonstrated. In addition, 2-phenoxyquinoxaline 1,4-di-N-oxide derivatives became 2-aminoquinoxaline 1,4-di-N-oxide derivatives in the presence of gaseous ammonia

Endotoxin-induced lung alveolar cell injury causes brain cell damage

Instituto de Salud Carlos III (ISCIII

Residential radon and characteristics of chronic obstructive pulmonary disease

It is not known whether residential radon exposure may be linked to the development of chronic obstructive pulmonary disease (COPD) and/or have an influence on the functional characteristics or exacerbations of COPD. The aim of this study was therefore to ascertain whether there might be an association between residential radon concentrations and certain characteristics of COPD. We analyzed COPD cases drawn from a case–control study conducted in an area of high radon exposure. Data were collected on spirometric pulmonary function variables, hospital admissions, and smoking. Radon measurements were taken using alpha-track-type CR-39 detectors individually placed in patients’ homes. All statistical analyses were performed using the IBM SPSS v22 computer software program. The study included 189 COPD cases (79.4% men; median age 64 years). The median radon concentration was 157 Bq/m3. No differences were found between radon concentration and sex, age or severity of breathing obstruction as measured by FEV1%. It should be noted, however, that 48.1% of patients with FEV1%  600 Bq/m3 exhibited no different characteristics in lung function. Exposure to radon does not appear to have an influence on the clinical characteristics of smokers and ex-smokers with COPD. As exposure to residential radon increases, there is no trend towards a worsening of FEV1%. Further studies are thus needed to analyze this possible association in never-smokers with COPDSpanish Society of Pneumology & Thoracic Surgery (Sociedad Española de Neumología y Cirugía Torácica—SEPAR), competitive Project Number 439, call 2018S

Quinoxaline 1,4-di-N-oxide and the Potential for Treating Tuberculosis

New drugs active against drug-resistant tuberculosis are urgently needed to extend the range of TB treatment options to cover drug resistant infections. Quinoxaline derivatives show very interesting biological properties (antibacterial, antiviral, anticancer, antifungal, antihelmintic, insecticidal) and evaluation of their medicinal chemistry is still in progress. In this review we report the properties and the recent developments of quinoxaline 1,4-di-N-oxide derivatives as potential anti-tuberculosis agents. Specific agents are reviewed that have excellent antitubercular drug properties, are active on drug resistant strains and non-replicating mycobacteria. The properties of select analogs that have in vivo activity in the low dose aerosol infection model in mice will be reviewed

Synthesis and biological evaluation of new quinoxaline derivatives as antioxidant and anti-inflammatory agents

We report the synthesis, anti-inflammatory and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave assisted methods have been used in order to optimize reaction times and to improve the yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase. Two of the best lipoxygenase inhibitors (compounds 7b and 8f) were evaluated as in vivo anti-inflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug

A Soft Computing System to Perform Face Milling Operations

In this paper we present a soft computing system developed to optimize the face milling operation under High Speed conditions in the manufacture of steel components like molds with deep cavities. This applied research presents a multidisciplinary study based on the application of neural projection models in conjunction with identification systems, in order to find the optimal operating conditions in this industrial issue. Sensors on a milling centre capture the data used in this industrial case study defined under the frame of a machine-tool that manufactures industrial tools. The presented model is based on a two-phase application. The first phase uses a neural projection model capable of determine if the data collected is informative enough. The second phase is focus on identifying a model for the face milling process based on low-order models such as Black Box ones. The whole system is capable of approximating the optimal form of the model. Finally, it is shown that the Box-Jenkins algorithm, which calculates the function of a linear system from its input and output samples, is the most appropriate model to control such industrial task for the case of steel tools

A Soft Computing System to Perform Face Milling Operations

In this paper we present a soft computing system developed to optimize the face milling operation under High Speed conditions in the manufacture of steel components like molds with deep cavities. This applied research presents a multidisciplinary study based on the application of neural projection models in conjunction with identification systems, in order to find the optimal operating conditions in this industrial issue. Sensors on a milling centre capture the data used in this industrial case study defined under the frame of a machine-tool that manufactures industrial tools. The presented model is based on a two-phase application. The first phase uses a neural projection model capable of determine if the data collected is informative enough. The second phase is focus on identifying a model for the face milling process based on low-order models such as Black Box ones. The whole system is capable of approximating the optimal form of the model. Finally, it is shown that the Box-Jenkins algorithm, which calculates the function of a linear system from its input and output samples, is the most appropriate model to control such industrial task for the case of steel tools

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

Derivados de 1,4-di-N-óxido de quinoxalina y enfermedades olvidadas

Las enfermedades olvidadas son un grupo de enfermedades infecciosas médicamente diversas entre las que se encuentran tuberculosis, malaria, leishmaniasis y la enfermedad de Chagas, que afectan a millares de personas en todo el mundo pero, principalmente, a la gente pobre en países en vías de desarrollo. Son un reto para la Salud Pública Internacional ya que no existen vacunas parar controlarlas y los medicamentos existentes para su tratamiento no son adecuados. La necesidad de buscar nuevas terapias económicamente accesibles para la población afectada es cada vez más urgente y palpable, lo que ha dado lugar a la puesta en marcha de nuevas iniciativas internacionales que buscan la erradicación de estas enfermedades. A lo largo de los años, nuestro grupo de investigación ha llevado a cabo el diseño y la síntesis, mediante métodos sintéticos sencillos y de bajo coste, de diversos derivados de 1,4-di-N-óxido de quinoxalina con el objetivo de encontrar nuevos líderes para el tratamiento de algunas enfermedades olvidadas. Como resultado de varios proyectos de investigación, se han desarrollado nuevas estructuras activas como agentes antituberculosos, antimaláricos, antichagas y, más recientemente, como agentes antileishmania. Este resumen presenta los resultados más importantes obtenidos en este campo, de los que se puede concluir que el núcleo de 1,4-di-N-óxido de quinoxalina representa un posible avance en la búsqueda de nuevos compuestos activos

New 3-methylquinoxaline-2-carboxamide 1,4-di-N-oxide derivatives as anti- Mycobacterium tuberculosis agents.

Mycobacterium tuberculosis (M.Tb) is a bacillus capable of causing a chronic and fatal condition in humans known as tuberculosis (TB). It is estimated that there are 8 million new cases of TB per year and 3.1 million infected people die annually. Thirty-six new amide quinoxaline 1,4-di-N-oxide derivatives have been synthesized and evaluated as potential anti-tubercular agents,obtaining biological values similar to the reference compound, Rifampin (RIF)