Antimicrobial resistance (AMR) has become a significant public health problem.

Lemon balm (Agastache mexicana) and rosemary (Rosmarinus officinalis) were dried using a mixed-mode solar dryer. A 2(3)-factorial design was carried out: operation mode (mesh shade and direct irradiance), airflow (natural convection and forced convection), and type of flat plate solar collector cover (polycarbonate and glass). The drying kinetics of lemon balm and rosemary ranged from 4.5 to 6.5 h and 4 to 7 h, respectively, according to the operation mode of the solar dryer. The highest percentage of antioxidant activity in the 2,2-diphenyl-1-picrylhydrazil tests was lemon balm, with values between 88% and 93% (100 mu g/mL), and rosemary, 88% and 92% (100 mu g/mL). When forced convection was applied, solar collector thermal efficiency increased from 3.97%-5.11% to 17.20%-24.75%, dryer efficiencies ranged from 4.78% to 6.05%, and drying efficiencies between 14.17% and 44.23%. The lowest color difference (6.01) for lemon balm was shown with the mesh shade, forced convection, and glass cover collector, and for rosemary, the lowest color difference (12.87) resulted from using the mesh shade and natural convection; according to the analysis of variance, the cover collector did not affect significantly the color difference. Dehydrated lemon balm and rosemary could be used as an additive for medicinal, gastronomic, and food preservative applications.

Herein we present a facile four-step synthetic method for the synthesis of novel 2-aryl-substituted 7,8-dihydroquinolin-6(5H)-ones as cytotoxic agents. The key step was the use of Mannich salts derived from acetophenones as a Michael acceptor in the reaction with cyclohexane-1,4-dione monoethylene acetal to give 1,5-dicarbonyl compounds that were treated with ammonium acetate to give the 7,8-dihydroquinolin-6(5H)-ones. The cytotoxic activity of the synthesized compounds was evaluated against seven cell lines. The observed data showed good selectivity for chronic myeloid leukemia line K-562. The synthetic route was simple and applicable to various functional group containing substrates. These types of compounds may be utilized as lead compounds in cancer research and drug discovery.

In this article, a one-pot methodology for the synthesis of flavanones "on-water" from simple starting materials is reported. The reaction proceeds in basic media (KOH), at room-temperature and in distilled water, during a period of 48 h with up to 96 % yields. In addition, most flavanones are obtained pure enough after a simple filtration procedure.

El estudio tuvo como objetivo comparar la exactitud de las pruebas o métodos de recuento de garrapatas ingurgitadas en hembras bovinas criadas bajo sistemas de producción extensiva. Se utilizaron 49 vacas adultas de los genotipos Criollo Ñeembucú, Pardo Suizo, Brangus y Nelore durante el estío en marzo de 2019. Se revisaron varias regiones corporales de manera secuencial mediante el método visual indirecto, palpatorio y finalmente el método directo, definido este último como patrón de referencia o gold standard. Para la estimación de los indicadores de validez y fiabilidad, comparación del comportamiento de las curvas de características operacionales del receptor (ROC) y pruebas de concordancia se recurrió al programa para análisis epidemiológico de datos tabulados Epidat 3.1. La sensibilidad y el valor predictivo negativo fueron marcadamente superiores para la prueba palpatoria. El deficiente valor del índice Kappa reveló que el acuerdo entre el método visual indirecto y directo fue debido al azar (p= 0.2097). En el método palpatorio, la curva ROC mostró un área mayor en comparación con el método visual indirecto. Los resultados de la prueba de homogeneidad de las áreas ROC revelaron que la diferencia en cuanto a la eficacia de ambas pruebas fue altamente significativa (p˂0.01), pudiéndose constatar la poca utilidad del método visual indirecto aplicado al recuento de garrapatas ingurgitadas en fase parásita, no así del método palpatorio.

A high-yielding total synthesis of the indole alkaloid prenostodione was completed in 4 steps and 44% overall yield from 1H-indole-3-carboxylic acid. The expedient syntheses of prenostodiones containing distinct substituents at the para position of the phenyl frame underscored the scope of this methodology. The cytotoxic activities of the tert-butyl esters of prenostodione analogues were tested using six tumor cell lines. Preliminary structure-activity studies revealed the importance of the identity of the aromatic substituent at the C-4 position for cytotoxic activity. The IC50 values of these compounds were found to compare satisfactorily with those of the commercially available drugs etoposide and cisplatin. Furthermore, the compounds with, respectively, -OMe (14d) and -NO2 (14f) groups at C-4 were more selective than these control compounds in PC-3, K-562, and MCF-7 cells. Also, computational studies were carried out to determine the ADMET profiles and passive membrane permeabilities of the compounds. The results suggested the promise of 14d and 14f as hit compounds for the development of new anticancer agents.

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL–1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.

Background Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Compounds including a sulfur-containing scaffold have been shown to be key scaffolds in various antituberculosis agents. Interestingly, the 3-hydroxy-3-phenyl-prop-2-enedithioic acids 11a-j have, to the best of our knowledge, not been previously described as antituberculosis agents. Purpose In the present study, we investigated the role of substituents attached to the phenyl ring of a 3-hydroxy-3-phenyl-prop-2-enedithioic acid scaffold (compounds 11a–j) in inhibiting the growth of M. tuberculosis strain H37Rv. Methods (Z)-3-hydroxy-3-(4-R-phenyl)-prop-2-enedithioic acids 11b–j, with R groups including various electron-donating or electron-withdrawing groups, were designed by structurally modifying the lead compound 11a. The syntheses of 11a–j involved each one-step procedure starting from the corresponding substituted acetophenone. Compounds 11a–j were tested against M. tuberculosis strain H37Rv to evaluate their bacterial growth inhibitory activities. ADMET profiles were predicted by employing three different methods. In addition, molecular docking studies were carried out, based on the molecular similarities of the synthesized compounds with ethionamide (5), on the active site of the M. tuberculosis H37Rv (3R)-hydroxyacyl-ACP (HadAB) dehydratase heterodimer. Results The antituberculosis activities of compounds 11a–j could be explained in terms of the presence of electron-donating or electron-withdrawing substituents on the aromatic ring of the substituted 3-hydroxy-3-phenyl)-prop-2-enedithioic acid core. The activity and selectivity index (SI) value of (Z)-3-hydroxy-3-(4-nitrophenyl)-prop-2-enedithioic acid 11e suggested that this compound could be used for the design of novel antituberculosis agents. Most of the synthesized molecules showed an acceptable ADME profile and a low probability of being toxic. Docking studies of 11d and 11e showed them forming hydrogen bonds with the ACys61 residue of the HadAB enzyme. Conclusion Our results suggested that the antituberculosis compound 11e could be used for the design of novel antituberculosis agents.

The study aimed to compare the accuracy of tests or methods for counting engorged ticks in cows reared under extensive production systems. In total, 49 adult cows of the Criollo Neembucu, Brown Swiss, Brangus and Nelore genotypes were used during the summer in March 2019. Several body regions were reviewed sequentially using the indirect visual method, palpatory and finally the direct method, defined the latter as the gold standard. To estimate the validity and reliability indicators, comparison of the behavior of the receiver operating characteristics curves (ROC) and concordance tests, the Epidat 3.1 program for epidemiological analysis of tabulated data was used. The sensitivity and negative predictive value were markedly higher for the palpatory test. The poor value of the Kappa index revealed that the agreement between the indirect and direct visual method was due to random (p=0.2097). In the palpatory method, the ROC curve showed a larger area compared to the indirect visual method. The results of the homogeneity test of the ROC areas revealed that the difference in the efficacy of both tests was highly significant (p<0.01), proving the limited usefulness of the indirect visual method applied to the count of engorged ticks in the parasitic phase, as opposed to the palpatory method.

. In molecular studies, having an excellent quantity and quality of DNA is essential. The aim of this study was to analyse two genomic DNA extraction methods based on the Chelex and Proteinase K protocols from whole blood samples, blood impregnated on filter paper and sheep hairs (n = 30 samples). The determination of quality and quantity of the DNA was carried out through spectrophotometry. To confirm the presence of amplified products, the extracted DNA was analysed by agarose gel electrophoresis and cPCR. The results showed a high level of variation for concentrations and purities of DNA, where the highest concentration of DNA was with the Proteinase K protocol from filter paper (151.75 ng / µl), while with the hair sample the lower means, both for Chelex (20.61 ng/µl) and Proteinase K (18.25 ng/µl). Regarding purity, the Chelex extraction method presented a higher frequency of contaminated samples (66%); while for the Proteinase K protocol, the highest purity values were found in the optimal (33%) and acceptable (27%) categories.

Bisindole photoactive molecules were developed with basis on the natural product caulerpin. These systems are applicable as photo-controllable molecular switches.

New derivatives of pyrroloazepinones were synthesized. The synthesis route consisted of three stages: the formation of a dimedone-derived tricarbonyl compound, the formation of a pyrrole ring resulting from the use of the Paal-Knorr method to generate tetrahydroindole-6-ones, and the expansion of the ketone by following the Schmidt method to generate lactams. The obtained 6-indolones were used to generate new derivatives: the pyrrolo[2,3-c]azepin-6-one and the pyrrolo[2,3-d]azepin-7-one ring systems. The synthesized pyrroloazepinones were evaluated for inhibitory activity in cancer cell lines and they did not show activity and cytotoxic effects on the non-tumor cells HEK239, with IC50 >= 215 +/- 5.41 mu M. [GRAPHICS] .

Acylthiosemicarbazides 8a-n were designed by structural modification of lead Compound 7. The syntheses of 8a-n involve a five-step procedure starting from carboxylic acids. Compounds 8a-n were tested against three Mycobacterium tuberculosis strains to measure their inhibitory antituberculosis activities. These activities could be explained according to the presence or absence of the chlorine substituent in the aromatic ring of the amide joined to the thiosemicarbazide core. Thiosemicarbazide derivative 8n is a candidate for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

Nitro-substituted heteroaromatic carboxamides 1a-e were synthesized and tested against three Mycobacterium tuberculosis cell lines. The activities can be explained in terms of the distribution of the electronic density across the nitro-substituted heteroaromatic ring attached to the amide group. 1,3,5-Oxadiazole derivatives 1c-e are candidates for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

Introducción: La fibrosis quística atípica (FQA) es una variante fenotípica de la fibrosis quística (FQ) que ocurre en los sujetos con clínica compatible con la FQ, con al menos una mutación compatible, pero en los que no se cumplen estrictamente los criterios diagnósticos de a FQ. Se ha propuesto recientemente que la medida de los ácidos grasos (por cromatografía de gases) de los fosfolípidos plasmáticos (AGFP) puede ser útil en el diagnóstico de la FQ; no obstante se desconoce su posible utilidad en la FQA. Material y métodos: Comparar las características clínicas, antropométricas, dietéticas, de laboratorio, espirométricas y radiológicas en sujetos adultos con FQ (n = 55) y en pacientes con FQA (n = 16). También seleccionamos a una muestra de adultos sanos (de igual sexo, edad y composición corporal) procedentes de un estudio poblacional para comparar el perfil de AGFP con los FQ y FQA. Resultados: Los sujetos con fibrosis quística atípica comparado con los pacientes con FQ, presentaron diferencias significativas en cuanto a la edad (24,0 ± 8,7 vs 36,6 ± 13,9), edad al diagnóstico (9,6 ± 12,9 vs 30,2 ± 26,5), test del sudor (condutividad mmol/l) (109 ± 13,4 vs 67,3 ± 22,2), NIH score (69 ± 21 vs 90 ± 11), Bahlla score (14,8 ± 4 vs 19,2 ± 3,5), FEV1(%)(59,6 ± 26,2 vs 78,9 ± 21,6), colesterol total (127 ± 26 vs 175,9 ± 32,7 mg/dl) e IMC (24,6 ± 5 vs 21,5 ± 4). No encontramos diferencias entre los pacientes con FQ y FQA en ninguno de los AGFP estudiados ni en la glucemia, insulinemia o péptido C. La ingesta calórica fue significativamente superior en los pacientes con FQ vs FQA, aunque la distribución calórica de los macronutrientes no fue diferente. Comparado con los controles, los porcentajes de los ácidos grasos (de los fosfolípidos séricos) esteárico y total de saturados fue significativamente mayor en los pacientes con FQ y con FQA, mientras que los niveles de docosahexaenoico, poliinsaturados totales, n-3 y n-6 fueron significativamente menores. Conclusiones: A pesar de que las características clínicas son claramente diferentes a los de la FQ típica, el perfil de los ácidos grasos de los fosfolípidos en suero es similar en ambas entidades y claramente diferente de los controles, por lo que no parece útil para diferenciar ambas entidades.

Abstract This paper describes several engineering workflows as part of the Digital Oil Field Solution implemented in a Gas Asset where there are different technical challenges. The main objective of this technology application is to revert the production decrease and optimize the operations in the asset, enhancing the capabilities of monitoring and surveillance and also to improve the analysis capability, taking the advantage of the benefits of the real time instrumentation, data integration, data quality, in addition to the definition of a complete automation process for all the information in different frequencies covering all the stages such as: data acquisition, transmission, integration, until monitoring and surveillance. With the implementation of operational and engineering workflows better efficiencies can be achieved, improving in time of response, and the decision making process, having tools for early anomaly detection to take proactively corrective actions that minimize the deferred production and losses.

ABSTRACT Preclinical Research The diterpene ent‐dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1–250 µM), and the antibacterial (50–1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1–100 mg/kg p.o.) and anti‐inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12 ‐O‐ tetradecanoylphorbol ‐ 13 ‐ acetate, respectively. The antinociceptive and sedative effects of DTA (1–100 mg/kg p.o.) were evaluated using two models of chemically‐induced nociception, and the pentobarbital‐induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10–100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC 50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti‐inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED 50 = 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED 50 =33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340‐348, 2017. © 2017 Wiley Periodicals, Inc.

Context: Gymnosperma glutinosum (Spreng.) Less. (Asteraceae) is a bush used for the empirical treatment of pain, fever, and cancer. An ent-neo-clerodane diterpene (2-angeloyl ent-dihydrotumanoic acid; ADTA) was isolated from G. glutinosum.Objective: This study evaluates the cytotoxic, anti-inflammatory, and antinociceptive effects of ADTA.Materials and methods: The cytotoxic effects of ADTA (1-350 mu M) were evaluated using the MTT assay with human tumorigenic (SW-620, MDA-MB231, SKLU1, SiHa, and PC-3), and non-tumorigenic (HaCaT) cells for 48 h. The in vitro anti-inflammatory effects of ADTA (0.23-460 mu M) were assessed using murine peritoneal macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The antinociceptive effects of ADTA (25-100mg/ kg p.o.) were evaluated using two in vivo models of chemical-induced nociception during 1 h.Results: ADTA lacked cytotoxic activity (IC50 > 100 mu M) on tumorigenic cells. In non-tumorigenic cells (HaCaT), ADTA exerted low cytotoxic effects (IC50 = 273 mu M). ADTA, at concentrations of 115 mu M or higher, decreased the release of pro-inflammatory mediators. The maximum antinociceptive effects of ADTA in the acetic acid-induced abdominal constrictions by ADTA was found at 100 mg/kg (63%), whereas in the formalin test at phase 1 and phase 2, ADTA (100 mg/kg) decreased the licking time by 47 and 71%, respectively.Conclusion: The results indicate that ADTA, obtained from G. glutinosum, exerts moderate in vitro anti-inflammatory and in vivo antinociceptive effects, but lacks cytotoxic effects on human cancer cells.

In this study, the pyrrolo[2,1-a]isoquinolines 4a-n were synthesized in good yields in a three steps synthesis from the corresponding α,β-unsaturated esters starting materials. These compounds were tested on six human cancer cells lines to measure the cytotoxic activity as a function of the electronic properties and aromaticity of the substituent at the C-2 position of the pyrroloisoquinoline. Our results reveal that the cytotoxic activity could be explained in terms of the distribution of electronic density across the ring joined to C-2. Also, this study identified 3-hydroxy (4d) and 3-chloro (4j) derivatives with powerful cytotoxic activities. The IC50 values of these compounds were found to be comparable to those of the commercially available Topotecan, Irinotecan, Etoposide, Tamoxifen, and Cisplatin.

Resumen. Se describe el análisis conformacional del compuesto nombrado en el título. Los resultados muestran que la conformación preferida no es la esperada a partir de consideraciones estéricas. El cambio de disolvente de CDCl3 a benceno-d6 no tuvo efecto significativo en el equilibrio. Palabras clave: Análisis conformacional, benceno 1,4-disubstituído, RMN 1H. Abstract. A conformational analysis of the title compound in solution is described. Results show that the preferred conformation is not the one expected from steric considerations. Change of the solvent from CDCl3 to benzene-d6 had no significant effect on the equilibrium.