Avaliação da cumarina e seus derivados como inibidores da Janus Quinase-3 usando modelo teórico

For several years, cancer has increased in the population, being one of the main causes of death worldwide. This clinical pathology is associated with the activation/release of various biomolecules, including the Janus kinase family (JAKs). It is important to mention that some studies indicate that some JAK inhibitors (ruxolitinib and tofacitinib) may have a significant effect on some autoimmune diseases and cancer; however, some of these drugs can produce secondary effects such as herpes zoster, infectious, acute respiratory distress and others. The aim of this study was to evaluate the interaction of coumarin and its derivatives (compounds 2 to 24) with the JAK-3 surface. In this way, the Interaction of coumarin and their derivatives with JAK-3 was determined using the 3pjc protein and either decernotinib or tofacitinib drugs as theoretical tools on DockinServer program. The results showed differences in the aminoacid residues involved in the interaction of coumarin and their derivatives with 3pjc protein surface compared with decernotinib and tofacitinib. Besides, the inhibition constant (Ki) for coumarin derivatives 7, 9 and 10 was lower compared with tofacitinib. However, Ki was lower for 2, 5, 7, 8, 9, 10, and 24 compared with decernotinib. In conclusion, the coumarin derivatives 2, 5, 7, 8, 9, 10, and 24 could be good alternatives as JAK-3 inhibitors to decrease cancer cells growth.    Desde hace varios años, el cáncer ha aumentado en la población, siendo una de las principales causas de muerte a nivel mundial. Esta patología clínica está asociada con la activación/liberación de varias biomoléculas, incluida la familia Janus kinase (JAKs). Es importante mencionar que algunos estudios indican que algunos inhibidores de JAK (ruxolitinib y tofacitinib) pueden tener un efecto significativo en algunas enfermedades autoinmunes y cáncer; sin embargo, algunos de estos medicamentos pueden producir efectos secundarios como herpes zoster, infeccioso, dificultad respiratoria aguda y otros. El objetivo de este estudio fue evaluar la interacción de la cumarina y sus derivados (compuestos 2 a 24) con la superficie JAK-3. Así, la interacción de la cumarina y sus derivados con JAK-3 se determinó utilizando la proteína 3pjc y los fármacos decernotinib o tofacitinib como herramientas teóricas en el programa DockinServer. Los resultados mostraron diferencias en los residuos de aminoácidos involucrados en la interacción de la cumarina y sus derivados con la superficie de la proteína 3pjc en comparación con decernotinib y tofacitinib. Además, la constante de inhibición (Ki) para los derivados de cumarina 7, 9 y 10 fue menor en comparación con tofacitinib. Sin embargo, Ki fue menor para 2, 5, 7, 8, 9, 10 y 24 en comparación con decernotinib. En conclusión, los derivados de cumarina 2, 5, 7, 8, 9, 10 y 24 pueden ser una buena alternativa como inhibidores de JAK-3 para disminuir el crecimiento de células cancerosas.    Há vários anos, o câncer tem aumentado na população, sendo uma das principais causas de morte em todo o mundo. Esta patologia clínica está associada à ativação/liberação de várias biomoléculas, incluindo a família Janus quinase (JAKs). É importante mencionar que alguns estudos indicam que alguns inibidores de JAK (ruxolitinib e tofacitinib) podem ter um efeito significativo em algumas doenças autoimunes e no câncer; no entanto, algumas dessas drogas podem produzir efeitos secundários, como herpes zoster, infeccioso, desconforto respiratório agudo e outros. O objetivo deste estudo foi avaliar a interação da cumarina e seus derivados (compostos 2 a 24) com a superfície JAK-3. Desta forma, a interação da cumarina e seus derivados com JAK-3 foi determinada usando a proteína 3pjc e as drogas decernotinib ou tofacitinib como ferramentas teóricas no programa DockinServer. Os resultados mostraram diferenças nos resíduos de aminoácidos envolvidos na interação da cumarina e seus derivados com a superfície da proteína 3pjc em comparação com decernotinib e tofacitinib. Além disso, a constante de inibição (Ki) para os derivados cumarínicos 7, 9 e 10 foi menor em comparação com o tofacitinibe. No entanto, Ki foi menor para 2, 5, 7, 8, 9, 10 e 24 em comparação com decernotinibe. Em conclusão, os derivados cumarínicos 2, 5, 7, 8, 9, 10 e 24 podem ser uma boa alternativa como inibidores de JAK-3 para diminuir o crescimento de células cancerígenas.  

Biochemical interaction of twenty steroid derivatives with ribosomal protein kinase 4 S6 (RSK-4) surface using a theoretical model

Several genetic expressions have been involved in the development of cancer such as the expression of a ribosomal kinase S6 P90 (RSK-4). It is important to mention that some compounds such as LJH685, 2073047-06-8, and SL0101 can act as RSK-4 inhibitors; however, its interaction with the surface of RSK-4 is very confusing. The aim of this research was to evaluate the interaction of twenty-nine steroid derivatives (1 to 29) with of RSK-4 surface using 6rv2 protein, LJH685, 2073047-06-8 and SL0101 as theoretical tools in the Dockingserver program. The results showed differences in the aminoacid residues involved in the interaction of steroid derivatives with 6rv2 protein surface compared with LJH685, 2073047-06-8 and SL0101. Besides, the inhibition constant for steroid derivatives 1, 12, 14, 19 and 22 was lower compared to 2073047-06-8 drug. In conclusion, the steroid derivatives 1, 12, 14, 19 and 22 could be a good alternative as RSK-4 inhibitors to decrease cancer cells growth

Actividad biológica del aceite de cocodrilo (Crocodylus moreletii)

La ingesta media de ácidos grasos poliinsaturados es insuficiente en el 50% de la población mexicana, teniendo una ingesta promedio de 30 mg/d. Diversas investigaciones señalan que los ácidos grasos poliinsaturados ejercen actividad inotrópica en el sistema cardiovascular, muchas de estas se han realizado utilizando diferentes especies marinas. A pesar de ello, se carecen de estudios relacionados con la caracterización y la evaluación de los efectos a la salud para la especie Crocodylus moreletii, endémica del Golfo de México. De acuerdo al perfil de ácidos grasos realizado mediante cromatografía de gases–espectrometría de masas, se reporta la presencia de 15 ácidos grasos, siendo un 25% grasa saturada, 54.4% grasa insaturada y 20.6% de otros compuestos grasos. Los cuales posiblemente tengan la capacidad para aumentar la presión de perfusión y un visible efecto cardioprotector ante daño por isquemia-reperfusión, en un modelo de corazón aislado y perfundido de rata.The average intake of polyunsaturated fatty acids is insufficient in 50% of the Mexican population, having an average intake of 30 mg/d. Research shows that polyunsaturated fatty acids perform inotropic activity in the cardiovascular system, many of which have been carried out using different marine species. However, there are no studies related to the characterization and evaluation of health effects for the species Crocodylus moreletii, endemic to the Gulf of Mexico. According to the profile of fatty acids performed by gas chromatography–mass spectrometry, the presence of 15 fatty acids is reported, being 25% saturated fat, 54.4% unsaturated fat and 20.6% other fatty compounds. They may have the ability to increase perfusion pressure and a visible cardioprotection effect against ischemia-reperfusion damage, in an isolated and perfused rat heart model

Design and Synthesis of an Indole-Estrogen Derivative

There are several methods reported for synthesis of aromatic-condensed derivatives; nevertheless, expensive reagents and special conditions are required. Therefore, in this study, an indole-estrogen derivative (3-[4-(2-butyl-3-cyclohexylimino-4-piperidin-1-yl-cyclobutylidencarbamoyl)]-phenoxy-NH-indolo[2′,3′:17,16]estra-1,3,5(10)triene) was synthesized using some strategies. The structure of all compounds obtained was confirmed by spectroscopic and spectrometric methods. In conclusion, a facile procedure for the formation of an indole-estrogen derivative was developed in this study

La intervención socioeducativa para el fortalecimiento de las comunidades

El artículo tiene como propósito pensar y recrear el debate en tornoa la intervención socioeducativa. Invita a resignificar las formas dela intervención. Se enfatiza en la necesidad de problematizardentro de un proceso donde el educador queda incluido, comosujeto de la experiencia. Se asume la intervención como una praxis intencionada, regulada por un coordinador grupal que se desempeña en un determinado rol de educador, promotor, terapeuta, investigador, mediador o facilitador. Se destacan la tradición reflexiva de Paulo Freire y Enrique Pichón Riviere, cuyos aportes reducen los inmensos peligros de una intervención socioeducativa instrumental

Design and synthesis of two triazonine-carbaldehyde derivatives using several chemical tools

Several triazonine-carbaldehyde derivatives have been prepared using different protocols; however, some require special reagents and conditions. The aim of study involved the synthesis of two triazonine-carbaldehyde derivative using testosterone or OTBS-testosterone as chemical tool. Triazonine-carbaldehyde derivatives were prepared by a series of reactions that involve the following: (1) synthesis of two nitrobenzamide derivatives by reaction of testosterone or OTBS-testosterone with p-nitrobenzoyl azide using Copper(II) as catalyst; (2) reaction of the nitrobenzamides with ethylenediamine to form two triazonine derivatives using boric acid as catalyst; (3) preparation of hexynyl-triazonine derivatives by the reaction of two triazonines 6-chlorohex-1-yne in basic medium; (4) reaction of hexynyl-triazonine derivatives with benzaldehyde to form two triazoninol analogs; (5) preparation of triazoninynal derivatives through oxidation of triazoninol analogs with dimethyl sulfoxide; and (6) synthesis of triazonine-carbaldehyde derivatives by the reaction of triazoninynal derivatives with hexyne-1 using Copper(II) as catalyst. The chemical structure of compounds was determined by spectroscopic and spectrometric methods. In conclusion, in this work were prepared two triazoninone derivatives using several chemical techniques, which are simple procedures and easy to handle

Design and synthesis of two triazonine-carbaldehyde derivatives using several chemical tools

AbstractSeveral triazonine-carbaldehyde derivatives have been prepared using different protocols; however, some require special reagents and conditions. The aim of study involved the synthesis of two triazonine-carbaldehyde derivative using testosterone or OTBS-testosterone as chemical tool. Triazonine-carbaldehyde derivatives were prepared by a series of reactions that involve the following: (1) synthesis of two nitrobenzamide derivatives by reaction of testosterone or OTBS-testosterone with p-nitrobenzoyl azide using Copper(II) as catalyst; (2) reaction of the nitrobenzamides with ethylenediamine to form two triazonine derivatives using boric acid as catalyst; (3) preparation of hexynyl-triazonine derivatives by the reaction of two triazonines 6-chlorohex-1-yne in basic medium; (4) reaction of hexynyl-triazonine derivatives with benzaldehyde to form two triazoninol analogs; (5) preparation of triazoninynal derivatives through oxidation of triazoninol analogs with dimethyl sulfoxide; and (6) synthesis of triazonine-carbaldehyde derivatives by the reaction of triazoninynal derivatives with hexyne-1 using Copper(II) as catalyst. The chemical structure of compounds was determined by spectroscopic and spectrometric methods. In conclusion, in this work were prepared two triazoninone derivatives using several chemical techniques, which are simple procedures and easy to handle

Design and Synthesis of Two Oxazine Derivatives Using Several Strategies

Several oxazine derivatives have been synthesized; nevertheless, expensive reagents and special conditions are required. Therefore, in this study, two oxazine derivatives (2-chloro-3-{{2-[-(3-chloro-2-oxo-cyclobutyl)-(2,3-dimethoxy-9,10-dihydrostrychnid-10-yl)-amino]-ethyl}-[1,5-dimethyl-4-(1H-naphtho[1,2-e][1,3-oxazin-2-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-yl]-amino}-cyclobutanone and 2-chloro-3-{{2-[(3-chloro-2-oxo-cyclobutyl)-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino]-ethyl}-[1,5-dimethyl-4-(1H-naphtho[1,2-e][1,3]oxazin-2-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-yl]-amino}-cyclobutanone) were synthesized using several strategies. The structure of compounds obtained was confirmed by elemental analysis, spectroscopy, and spectrometry data. In conclusion, the methods used offer some advantages such as good yields, simple procedure, low cost, and ease of workup

Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases P=0.05 the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited P=0.06 by indomethacin and PINANE-TXA2  P=0.05 at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation