A Metastable Semiquinone Molecular Switch Modulated by Ascorbate/O2: A Study from a System Far-From-Equilibrium to Biological Assays in Mitochondria.

A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

HLA-DRB1 and HLA-DQB1 genes in patients diagnosed with systemic lupus erythematosus in Guatemala.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that impacts connective tissue and can affect various organs and systems within the body. One important aspect of this disease is the role of the human leukocyte antigen (HLA) system, a protein complex that plays a role in the immune response. Specifically, the HLA-DRB1 and HLA-DQB1 genes have been implicated in the development of SLE. In order to better understand this relationship in the Guatemalan population, a study was conducted with the objective of characterizing the allelic and haplotype profiles of the HLA-DQB1 and HLA-DRB1 loci in 50 patients diagnosed with SLE who were receiving treatment at a hospital in Guatemala. Allele and haplotype frequencies were determined and compared to 127 healthy Guatemalan subjects as a control group. The results of the analysis showed a reduction in the frequencies of HLA-DQB1*03 and HLA-DRB1*14 in SLE patients, which could suggest a protective effect on the development of the disease. In contrast, a risk association was found between HLA-DRB1*07, HLA-DRB1*08, HLA-DQB1*02 and HLA-DQB1*06 in SLE patients. Finally, we observed an additional protective associated of haplotype HLA-DRB1*04∼DQB1*03 with SLE patients, while haplotypes HLA-DRB1*07∼DQB1*02 and DRB1*08-DQB1*06 showed a risk association.

Vasodilator activity of Poecilotheria ornata venom involves activation of the NO/cGMP pathway and inhibition of calcium influx to vascular smooth muscle cells.

Tarantula venoms may be a natural source of new vasodilator components useful in pharmacological research. Moreover, biological function data of the venoms are important to enhance the knowledge about the biodiversity and evolution of these species. The present study aims to describe the vasodilatory activity induced by the venom of Poecilotheria ornata on isolated rat aortic rings. This venom induced a vasodilator activity that was significantly reduced after incubation with L-NAME or ODQ. Measurements of nitrite concentrations on rat aorta homogenates showed that the venom significantly increased the basal levels. Moreover, the venom attenuates the contraction induced by calcium. These results suggest that P. ornata venom contains a mixture of vasodilator components that act through the activation of the nitric oxide/cGMP pathway, as well as, through an endothelium-independent mechanism that involves the calcium influx into vascular smooth muscle cells.

Portland Cement-Based Grouts Enhanced with Basalt Fibers for Post-Tensioned Concrete Duct Filling.

In post-tensioned systems, grouts act as a last line of defense to prevent the penetration of harmful compounds such as chlorides, moisture and other substances that cause corrosion in the prestressing steel. For this reason, improving grouts results in the enhancement of the overall durability of the structure. In this study, the physical properties of grouts with basalt microfiber additions in the amounts of 0.03, 0.07 and 0.10% with respect to the mix volume were evaluated. The fresh properties included flowability and unit mass. Specimens were fabricated to evaluate drying shrinkage, compressive strength, air permeability and rapid permeability to chloride ions. The incorporation of basalt microfibers showed a beneficial effect on the physical properties of the grout by increasing the drying shrinkage resistance and decreasing the permeability compared to the reference mix and two commercial dry prepackaged grouts. The optimal grout mix was the one with a percentage of basalt microfibers of 0.10%, which decreased drying shrinkage by 15.98% at 14 days compared to the reference mix, and permeability to chloride ions decreased by 10.82% compared to the control mix.

A subfraction obtained from the venom of the tarantula Poecilotheria regalis contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels.

Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds. However, only two peptides isolated from spider venoms have been investigated so far. This study describes for the first time a subfraction containing inhibitor cystine knot peptides, PrFr-I, obtained from the venom of the tarantula Poecilotheria regalis. This subfraction induced sustained vasodilation in rat aortic rings independent of vascular endothelium and endothelial ion channels. Furthermore, PrFr-I decreased calcium-induced contraction of rat aortic segments and reduced extracellular calcium influx to chromaffin cells by the blockade of L-type voltage-gated calcium channels. This mechanism was unrelated to the activation of potassium channels from vascular smooth muscle, since vasodilation was not affected in the presence of TEA, and PrFr-I did not modify the conductance of the voltage-gated potassium channel Kv10.1. This work proposes a new envenomating function of peptides from venoms of tarantulas, and establishes a new mechanism for venom-induced vasodilation.

Metformin, a biological and synthetic overview.

Metformin is the most widely known anti-hyperglycemic, officially acquired by the USA government in 1995 and in 2001 it became the most prescribed treatment for type II diabetes. But how did it become the must-use drug for this disease in such a short period of time? it all started with traditional medicine, by using a plant known as "goat's rue" for the reduction of blood glucose levels. Its use arose in 1918 and evolved to the metformin synthesis in laboratories a couple of years later, using very rudimentary methods which involved melting and strong heating. Thus, a first synthetic route that allowed the preparation of the initial metformin derivates was established. Some of these resulted toxics, and others outperformed the metformin, reducing the blood glucose levels in such efficient way. Nevertheless, the risk and documented cases of lactic acidosis increased with metformin derivatives like buformin and phenformin. Recently, metformin has been widely studied, and it has been associated and tested in the treatment of type II diabetes, cancer, polycystic ovarian syndrome, cell differentiation to oligodendrocytes, reduction of oxidative stress in cells, weight reduction, as anti-inflammatory and even in the recent COVID-19 disease. Herein we briefly review and analyze the history, synthesis, and biological applications of metformin and its derivates.

Role of the nonribosomal peptide synthetase siderophore enzyme (Rfs) of Mucor lusitanicus in controlling the growth of fungal phytopathogens.

Dimorphic species of Mucor, which are cosmopolitan fungi belonging to subphylum Mucoromycotina, are metabolically versatile. Some species of Mucor are sources of biotechnological products, such as biodiesel from Mucor circinelloides and expression of heterologous proteins from Mucor lusitanicus. Furthermore, Mucor lusitanicus has been described as a model for understanding mucormycosis infections. However, little is known regarding the relationship between Mucor lusitanicus and other soil inhabitants. In this study, we investigated the potential use of Mucor lusitanicus as a biocontrol agent against fungal phytopathogens, namely Fusarium oxysporum f. sp. lycopersici, Fusarium solani, and Alternaria solani, which destroy economically important crops. Results showed that aerobic cell-free supernatants of the culture broth (SS) from Mucor lusitanicus inhibited the growth of the fungal phytopathogens in culture, soil, and tomato fruits. The SS obtained from a strain of Mucor lusitanicus carrying the deletion of rfs gene, which encodes an enzyme involved in the synthesis of siderophore rhizoferrin, had a decreased inhibitory effect against the growth of the phytopathogens. Contrarily, this inhibitory effect was more evident with the SS from an rfs-overexpressing strain compared to the wild-type. This study provides a framework for the potential biotechnological use of the molecules secreted from Mucor lusitanicus in the biocontrol of fungal phytopathogens.

Transcriptomic differences between bleached and unbleached hydrozoan Millepora complanata following the 2015-2016 ENSO in the Mexican Caribbean.

The 2015-2016 El Niño-southern oscillation or "ENSO" caused many M. complanata colonies that live in the Mexican Caribbean to experience extensive bleaching. The purpose of this work was to analyze the effect of bleaching on the cellular response of M. complanata, employing a transcriptomic approach with RNA-seq. As expected, bleached specimens contained a significantly lower chlorophyll content than unbleached hydrocorals. The presence of algae of the genera Durusdinium and Cladocopium was only found in tissues of unbleached M. complanata, which could be associated to the greater resistance that these colonies exhibited during bleaching. We found that 299 genes were differentially expressed in M. complanata bleached colonies following the 2015-2016 ENSO in the Mexican Caribbean. The differential expression analysis of bleached M. complanata specimens evidenced enriched terms for functional categories, such as ribosome, RNA polymerase and basal transcription factors, chaperone, oxidoreductase, among others. Our results suggest that the heat-shock response mechanisms displayed by M. complanata include: an up-regulation of endogenous antioxidant defenses; a higher expression of heat stress response genes; up-regulation of transcription-related genes, higher expression of genes associated to transport processes, inter alia. This study constitutes the first differential gene expression analysis of the molecular response of a reef-forming hydrozoan during bleaching.

Development of a Portland Cement-Based Material with Agave salmiana Leaves Bioaggregate.

Depending on the morphology of the natural fibers, they can be used as reinforcement to improve flexural strength in cement-based composites or as aggregates to improve thermal conductivity properties. In this last aspect, hemp, coconut, flax, sunflower, and corn fibers have been used extensively, and further study is expected into different bioaggregates that allow diversifying of the raw materials. The objective of the research was to develop plant-based concretes with a matrix based on Portland cement and an aggregate of Agave salmiana (AS) leaves, obtained from the residues of the tequila industry that have no current purpose, as a total replacement for the calcareous aggregates commonly used in the manufacturing of mortars and whose extraction is associated with high levels of pollution, to improve their thermal properties and reduce the energy demand for air conditioning in homes. Characterization tests were carried out on the raw materials and the vegetal aggregate was processed to improve its compatibility with the cement paste through four different treatments: (a) freezing (T/C), (b) hornification (T/H), (c) sodium hydroxide (T/NaOH), and (d) solid paraffin (T/P). The effect of the treatments on the physical properties of the resulting composite was evaluated by studying the vegetal concrete under thermal conductivity, bulk density, and compressive strength tests with a volumetric ratio between the vegetal aggregate and the cement paste of 0.36 and a water/cement ratio of 0.35. The hornification treatment showed a 15.2% decrease in the water absorption capacity of the aggregate, resulting in a composite with a thermal conductivity of 0.49 W/mK and a compressive strength of 8.66 MPa, which allows its utilization as a construction material to produce prefabricated blocks.

Percepción social del SARS-CoV-2 en la mirada de una comunidad rural / Social perception of SARS-CoV-2 in the view of a rural community

Introducción: en la actual pandemia por COVID-19, las megalópolis han sido un foco importante de atención por la densidad poblacional con la que cuentan, dado que esta impacta directamente en el número de contagios registrados; sin embargo, el riesgo al que se enfrentan las comunidades rurales es alto y algunas veces desconocido, debido a sus características históricas, geográficas y por su distribución de bienes. Objetivo: interpretar la percepción social de la pandemia por SARS-CoV-2 de los habitantes de una comunidad rural. Metodología: investigación cualitativa, fenomenológica e interpretativa, realizada en dos etapas. En la primera se hizo trabajo de campo exploratorio y en la segunda se utilizó como técnica de recolección de datos una entrevista semiestructurada para siete habitantes, apoyada en una guía de preguntas. El análisis de los datos se basó en la transcripción, lectura, codificación, formación de categorías y subcategorías. Los criterios de rigor científico fueron la credibilidad y la confirmabilidad. Resultados: se construyeron cinco temas: Ver para creer, Desconfianza, Miedo, Canales de aprendizaje y Zona de protección, cada uno con sus respectivos subtemas. Conclusiones: la percepción social es de vital importancia al permitir interpretar el afrontamiento, debilidades y fortalezas de las comunidades rurales ante la COVID-19; generar conocimiento en este campo es relevante para la creación de herramientas y estrategias que ayuden a los sistemas de salud y a los profesionales sanitarios; en el caso de enfermería, su acción comunitaria es primordial para prevenir la propagación del SARS-CoV-2.

Introduction: In the current COVID-19 pandemic, supercities have been an important focus of attention due to the population density, since this has an impact on the number of registered infections; however, the risk faced by rural communities is high and sometimes unknown due to its historical and geographical characteristics and its distribution of assets. Objective: To interpret the social perception of the SARS-CoV-2 pandemic of the inhabitants of a rural community. Methodology: Qualitative, phenomenological and interpretive research, carried out in two stages. In the first one, exploratory field work was done and in the second stage, as a data collection technique, a semi-structured interview with seven inhabitants was used, supported by a question guide. The data analysis was based on the transcription, reading, coding, formation of categories and subcategories. The criteria for scientific rigor were credibility and confirmability. Results: Five themes were constructed: Seeing is believing, Distrust, Fear, Learning channels and Protection zone, each with their respective subtopics. Conclusions: Social perception is of vital importance, since it allows interpreting the coping, weaknesses and strengths of rural communities in the face of COVID-19; generating knowledge in this field is relevant for the creation of tools and strategies that help health systems and health professionals; in the case of nursing, their community action is essential to prevent the spread of SARS-CoV-2.

Anti-SARS-CoV-2 IgG antibodies pre- and post-vaccination behavior in health workers from a Guatemalan cancer center.

INTRODUCTION: The study of anti-SARS-CoV-2 IgG antibodies allows asymptomatic individuals with COVID-19 to be identified, and post-infection and post-vaccination immunity status to be evaluated. OBJECTIVE: To know the behavior of anti-SARS-CoV-2 IgG antibodies before and after vaccination in workers of a cancer center. METHODS: Prior to the application of the vaccine, the presence of anti-SARS-CoV-2 IgG antibodies (n = 171) was analyzed by evaluating anti-N IgG antibodies; post-vaccination, after receiving the second dose, anti-S IgG antibodies were evaluated (n = 60). RESULTS: Prior to vaccination, IgG antibodies were present in 18.71% of participants; they were detected in 65.22% of those with prior history of COVID-19 diagnosis and in 11.49% of those without it. The positions with the highest prevalence were nurses (28.26%), paramedics (27.59%) and administrative workers (27.78%), p < 0.01. Anosmia, ageusia and chest tightness were associated with the presence of IgG (p < 0.05). Post-vaccination, all participants developed IgG antibodies; people with a previous COVID-19 diagnosis had higher titers: 10,277 vs. 6,819 AU/mL, p < 0.001. CONCLUSIONS: The study of anti-SARS-CoV-2 IgG antibodies allowed asymptomatic health workers to be identified. A high percentage of participants with prior COVID-19 diagnosis had antibodies. All participants developed IgG antibodies after vaccination, with higher titers being identified in those with previous infection.

INTRODUCCIÓN: El estudio de anticuerpos IgG anti-SARS-CoV-2 permite identificar individuos asintomáticos con COVID-19 y evaluar la inmunidad posinfección y posvacunación. OBJETIVO: Conocer el comportamiento de los anticuerpos IgG anti-SARS-CoV-2 pre y posvacunación en trabajadores de un centro oncológico. MÉTODOS: Antes de aplicar la vacuna se analizaron los anticuerpos IgG anti-SARS-CoV-2 (n = 171) con la evaluación de IgG anti-N; después de la segunda dosis se evaluó IgG anti-S (n = 60). RESULTADOS: Prevacunación, los anticuerpos IgG estaban presentes en 18.71 % de los participantes; se detectaron en 65.22 % de aquellos con antecedente de diagnóstico de COVID-19 y en 11.49 % de aquellos sin antecedentes. Los profesiones con mayor prevalencia fueron enfermeros (28.26 %), paramédicos (27.59 %) y administrativos (27.78 %), p < 0.01. La anosmia, ageusia y opresión en el pecho se asociaron a la presencia de IgG (p < 0.05). Posvacunación, todos los participantes desarrollaron IgG; las personas con diagnóstico previo de COVID-19 presentaron mayores títulos: 10 277 versus 6819 UA/mL, p < 0.001. CONCLUSIONES: El estudio de anticuerpos IgG anti-SARS-CoV-2 permitió identificar a trabajadores de salud asintomáticos. Un alto porcentaje de los participantes con diagnóstico previo de COVID-19 presentó anticuerpos. Todos los participantes desarrollaron anticuerpos IgG posvacunación; las personas con infección previa presentaron una cuantificación más alta de títulos.

Iodine(III) reagents for oxidative aromatic halogenation.

Iodine(III) reagents have attracted chemical relvance in organic synthesis by their use as safe, non-toxic, green and easy to handle reagents in different transformations. These characteristics make them important alternatives to procedures involving hazardous and harsh reaction conditions. Their versatility as oxidants has been exploited in the functionalization of different aromatic cores, which allow the introduction of several groups. Metal-free arylation using iodine(III) reagents is by far one of the most described topics in the literature; however, other highly relevant non-aromatic groups have been also introduced. Herein, we summarize the most representative developed procedures for the functionalization of aryls and heteroaryls by introducing halogens, using different iodine(III) reagents.

Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)

Comportamiento de anticuerpos IgG anti-SARS-CoV-2 en trabajadores de salud pre y posvacunación en un centro oncológico de Guatemala / Anti-SARS-CoV-2 IgG antibodies pre- and post-vaccination behavior in health workers from a Guatemalan cancer center

Resumen Introducción: El estudio de anticuerpos IgG anti-SARS-CoV-2 permite identificar individuos asintomáticos con COVID-19 y evaluar la inmunidad posinfección y posvacunación. Objetivo: Conocer el comportamiento de los anticuerpos IgG anti-SARS-CoV-2 pre y posvacunación en trabajadores de un centro oncológico. Métodos: Antes de aplicar la vacuna se analizaron los anticuerpos IgG anti-SARS-CoV-2 (n = 171) con la evaluación de IgG anti-N; después de la segunda dosis se evaluó IgG anti-S (n = 60). Resultados: Prevacunación, los anticuerpos IgG estaban presentes en 18.71 % de los participantes; se detectaron en 65.22 % de aquellos con antecedente de diagnóstico de COVID-19 y en 11.49 % de aquellos sin antecedentes. Los profesiones con mayor prevalencia fueron enfermeros (28.26 %), paramédicos (27.59 %) y administrativos (27.78 %), p < 0.01. La anosmia, ageusia y opresión en el pecho se asociaron a la presencia de IgG (p < 0.05). Posvacunación, todos los participantes desarrollaron IgG; las personas con diagnóstico previo de COVID-19 presentaron mayores títulos: 10 277 versus 6819 UA/mL, p < 0.001. Conclusiones: El estudio de anticuerpos IgG anti-SARS-CoV-2 permitió identificar a trabajadores de salud asintomáticos. Un alto porcentaje de los participantes con diagnóstico previo de COVID-19 presentó anticuerpos. Todos los participantes desarrollaron anticuerpos IgG posvacunación; las personas con infección previa presentaron una cuantificación más alta de títulos.

Abstract Introduction: The study of anti-SARS-CoV-2 IgG antibodies allows asymptomatic individuals with COVID-19 to be identified, and post-infection and post-vaccination immunity status to be evaluated. Objective: To know the behavior of anti-SARS-CoV-2 IgG antibodies before and after vaccination in workers of a cancer center. Methods: Prior to the application of the vaccine, the presence of anti-SARS-CoV-2 IgG antibodies (n = 171) was analyzed by evaluating anti-N IgG antibodies; post-vaccination, after receiving the second dose, anti-S IgG antibodies were evaluated (n = 60). Results: Prior to vaccination, IgG antibodies were present in 18.71% of participants; they were detected in 65.22% of those with prior history of COVID-19 diagnosis and in 11.49% of those without it. The positions with the highest prevalence were nurses (28.26%), paramedics (27.59%) and administrative workers (27.78%), p < 0.01. Anosmia, ageusia and chest tightness were associated with the presence of IgG (p < 0.05). Post-vaccination, all participants developed IgG antibodies; people with a previous COVID-19 diagnosis had higher titers: 10,277 vs. 6,819 AU/mL, p < 0.001. Conclusions: The study of anti-SARS-CoV-2 IgG allowed asymptomatic health workers to be identified. A high percentage of participants with prior COVID-19 diagnosis had antibodies. All participants developed IgG after vaccination, with higher titers being identified in those with previous infection.

Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells.

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4H-benzo[d][1,3]oxazines has been developed starting from N-(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6-exo-dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4H-benzo[d][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4H-benzo[d][1,3]oxazines showed an IC50 ranking from 3.1 to 95 µM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.

Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the Csp2-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.

New Insights into the Toxin Diversity and Antimicrobial Activity of the "Fire Coral" Millepora complanata.

To date, few studies have been carried out aimed at characterizing the toxins synthesized by hydrocorals of the genus Millepora. The purpose of this study was to explore the toxin diversity and antibacterial activity of the "fire coral" M. complanata using a transcriptomic data mining approach. In addition, the cytolytic and antibacterial activities of the M. complanata nematocyst proteome were experimentally confirmed. Cytolysins were predicted from the transcriptome by comparing against the Animal Toxin Annotation Project database, resulting in 190 putative toxins, including metalloproteases, hemostasis-impairing toxins, phospholipases, among others. The M. complanata nematocyst proteome was analyzed by 1D and 2D electrophoresis and zymography. The zymograms showed different zones of cytolytic activity: two zones of hemolysis at ~25 and ~205 kDa, two regions corresponding to phospholipase A2 (PLA2) activity around 6 and 25 kDa, and a proteolytic zone was observed between 50 and 205 kDa. The hemolytic activity of the proteome was inhibited in the presence of PLA2 and proteases inhibitors, suggesting that PLA2s, trypsin, chymotrypsin, serine-proteases, and matrix metalloproteases are responsible for the hemolysis. On the other hand, antimicrobial peptide sequences were retrieved from their transcripts with the amPEPpy software. This analysis revealed the presence of homologs to SK84, cgUbiquitin, Ubiquicidin, TroTbeta4, SPINK9-v1, and Histone-related antimicrobials in the transcriptome of this cnidarian. Finally, by employing disk diffusion and microdilution assays, we found that the nematocyst peptidome of M. complanata showed inhibitory activity against both Gram-positive and Gram-negative bacteria including S. enteritidis, P. perfectomarina, E. coli, and C. xerosis, among others. This is the first transcriptomic data mining analysis to explore the diversity of the toxins synthesized by an organism of the genus Millepora. Undoubtedly, this work provides information that will broaden our general understanding of the structural richness of cnidarian toxins.

Myristic acid reduces skin inflammation and nociception.

This study evaluated the inhibitory effect of myristic acid (MA) on models of inflammation and nociception. The in vitro anti-inflammatory activities of MA were assessed on LPS-stimulated macrophages, membrane stabilization assay, and inhibition of protein denaturation, whereas the inhibitory activity of MA on in vivo inflammation was assessed on TPA-induced ear edema using acute and chronic assays in mice. The inhibitory effect of MA on nociception was assessed using three in vivo models. MA exerted in vitro anti-inflammatory activity by the increase (58%) in the production of IL-10 in LPS-stimulated macrophages. In the in vivo assay, MA showed good anti-inflammatory effects on the acute (ED50 = 62 mg/kg) and chronic (ED50 = 77 mg/kg) TPA-induced ear edema. The antinociceptive activity of MA was related to the participation of the nitrergic system in the formalin-induced paw licking test. PRACTICAL APPLICATIONS: Previous studies with different plant extracts containing MA, as one of their major components, have demonstrated anti-inflammatory and antinociceptive actions. However, the anti-inflammatory and antinociceptive actions of myristic acid have not been previously reported. The results suggest that MA induced anti-inflammatory effects in LPS-stimulated macrophages through the participation of IL-10. The antinociceptive effects of MA are attributed to the participation of the nitrergic system.