Resumen La carne de cerdo es uno de los productos más consumidos a nivel mundial, y los microorganismos patógenos en la carne de cerdo, como las Enterobacterias, representan un riesgo para la salud pública, provocando enfermedades de transmisión alimentaria. Las Enterobacterias en el procesamiento de la carne de cerdo son un indicador de una gestión sanitaria deficiente. Escherichia coli (E. coli) y Salmonella spp. son las bacterias más prevalentes. Diferentes estudios indican que su porcentaje alto y la multifarmaco-resistencia son un riesgo alarmante para la salud de los consumidores.

Summary Pork meat is one of the most consumed products worldwide, and pathogenic microorganisms in pork, such as Enterobacteriaceae, represent a public health risk, causing foodborne diseases. Enterobacteriaceae in pork meat processing is an indicator of poor sanitation management. Escherichia coli (E. coli) and Salmonella spp. are the most prevalent bacteria. Different studies report that their high percentage and the multidrug resistance found are an alarming risk to consumers´ health.

ABSTRACT Cypermethrin (CYP) is an insecticide pyrethroid used in the agriculture for its broad-spectrum activity. However, recent studies have shown the accumulation of CYP in soil, and water and a high toxicity against different species, including humans. On the other hand, the use of bacteria in bioremediation represents an eco-friendly alternative for the removal of different xenobiotics. In this study, the aim was to isolate and identify bacteria from agricultural soils to determine their ability to tolerate and biodegrade CYP. Additionally, some metabolites of the CYP biodegradation were detected by ultra-performance liquid chromatography with mass spectrometry (UPLC-MS). Klebsiella pneumoniae YH43 isolate used CYP as a carbon source, degrading 87.55 % at a concentration of 100 mg/L. α-cyano-3-phenoxybenzyl alcohol and cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate were identified as the main metabolites in the pathway of the CYP biodegradation. These results suggest that K. pneumoniae YH43 has the potential to be used in the bioremediation of contaminated soils with CYP.

RESUMEN La cipermetrina (CYP) es un insecticida piretroide utilizado en la agricultura por su actividad de amplio espectro. Sin embargo, estudios recientes han evidenciado la acumulación de CYP en suelo y agua y una alta toxicidad en diferentes especies, incluido el ser humano. Por otra parte, el uso de bacterias en la biorremediación representa una alternativa sostenible para la remoción de distintos xenobióticos. En este estudio, el objetivo fue aislar e identificar bacterias de suelos agrícolas con habilidad para tolerar y biodegradar CYP. Adicionalmente, varios metabolitos de la degradación de CYP fueron identificados por cromatografía de líquidos de ultra alta resolución con espectrometría de masas (UPLC-MS, por su sigla en inglés). Klebsiella pneumoniae YH43 usó a CYP como fuente de carbono, causando una degradación del 87.55 % a una concentración de 100 mg/L. El alcohol α-ciano-3-fenoxibencil y el carboxilato de cis,trans-3-(2,2-diclorovinil)-2,2-dimetilciclopropano fueron los principales metabolitos identificados en la ruta de degradación de CYP. Los resultados sugieren que Klebsiella pneumoniae YH43 tiene potencial para ser utilizada en la biorremediación de suelos contaminados con CYP.

Abstract Phthalimide is considered a scaffold for the development of new anticancer agents. In this work, the antiproliferative activity of forty-three phthalimide derivatives was evaluated against cervical (HeLa), liver (HepG2), breast (4T1) cancer cell lines, and a normal cell line of murine fibroblasts (3T3). Finally, a molecular docking analysis of phthalimide derivatives on the active site of the enzymes DNA methyltransferase 1 (DNMT1) and vascular endothelial growth factor receptor 2 (VEGR2) as potential drug targets was performed. The compounds, C16, E11, and E16 showed the best antiproliferative activity against the cell lines HeLa and 4T1. Only, the compound H16 decreased 32% cell proliferation against HepG2 cell line. The compounds H5, H16, E2, E16, and C1 did not affect the proliferation of the 3T3 cell line. The molecular docking analysis showed that phthalimide derivatives have a greater affinity for DNMT1 than S-adenosyl-l-homocysteine, a potent DNMT1 inhibitor. However, molecular docking results do not correlate with their antiproliferative effects, suggesting another potential mechanism of action for the active compounds.

Resumen Laestructura de la ftalimida esconsiderada un bloque de construcción para el desarrollo de nuevos agentes anticancerígenos. En este trabajo, se evaluó la actividad antiproliferativa de cuarenta y tres derivados de ftalimida contra las líneas celulares cancerígenas de cérvix (HeLa), hígado (HepG2), mama (4T1), y la línea celular normal de fibroblastos murinos (3T3). Por último, se realizó un análisis de acoplamiento molecular de los derivados de la ftalimida en el sitio activo de la enzima metiltransferasa 1 de DNA (DNMT1, por sus siglas en inglés) y el receptor del factor de crecimiento endotelial vascular 2 (VEGR2, por sus siglas en inglés) como posibles blancos farmacológicos. Los compuestos C16, E11 y E16 mostraron la mejor actividad antiproliferativa contra las líneas celulares HeLa y 4T1. Solamente, el compuesto H16 disminuyó 32% la proliferación celular de la línea HepG2. Los compuestos H5, H16, E2, E16 y C1 no afectaron la proliferación celular de la línea 3T3. El análisis de acoplamiento molecular demostró que los derivados de la ftalimida tienen una mayor afinidad que la S-adenosil-l-homocisteína, un potente inhibidor de la metiltransferasa 1 de DNA. Sin embargo, los resultados del acoplamiento molecular no se correlacionan con los efectos antiproliferativos; lo cual sugiere que los compuestos activos tienen otro mecanismo de acción.

A bioactive N,N-diacetylglycine (NNDAG) and new organotin(IV) complexes (OTCs) (1-7) were synthesized. Spectroscopic techniques were employed to characterize NNDAG and OTCs. FTIR was employed to verify N,N protection of glycine by acetyl groups. The disappearance of υ(OH) at 3000-2600 cm-1 showed de-protonation of free ligand. The Δυ 150<200 cm-1 of OTCs 4-7 verified bidentate coordination with tetrahedral geometry. The Δυ of OTCs1 and 3 was <200 cm-1 exhibitingtrans -octahedral geometry while OTC 2 dimer was assigned a unique sinusoidal view. The 1H NMR spectra of OTCs verified their synthesis by de-protonation of NNDAG and no chemical shift was found downfield for carboxylic acid proton. The 13C, 119Sn NMR and Mass spectrometric data also supported FTIR and 1H NMR descriptions. The OTCs 4, 5, 6 and7 (500 ppm) proved twice as active against Escherichia coli as the standard antibiotic enoxacin (1000 ppm). The promising property of the OTCs (4, 5, 6 and7) is clearly due to their tetrahedral. The OTCs 4and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum.LD50 of all the compounds were determined and OTCs4, 5 and 7 were found to be active.

Abstract: Tuberculosis is a major infectious disease in the world, which causes high mortality. The treatment consists of drugs of first and second line; however, its effectiveness is limited by several factors, mainly the presence of resistant and/or multi-drug resistant strains. This work reviews compounds derived from quinoxaline 1,4-dioxide with antimycobacterial activity in in vitro and in vivo models as an option for the development of new drugs against tuberculosis.

Resumen: La tuberculosis es una de las principales enfermedades infecciosas en el mundo, la cual causa una alta mortalidad. Su tratamiento consta de fármacos de primera y segunda línea, sin embargo, su eficacia se ve limitada por diversos factores, principalmente la presencia de cepas resistentes o multi-resistentes a los fármacos empleados. En este trabajo se revisó una serie de compuestos derivados de 1,4-dióxido de quinoxalina con actividad antimicobacteriana en modelos in vitro e in vivo como una opción para el desarrollo de nuevos fármacos contra la tuberculosis.

This paper briefly describes the progress that our research group has achieved in the design, synthesis and biological evaluation of new potential therapeutic molecules for public health problems such as obesity, cancer, tuberculosis, and American trypanosomiasis or Chagas disease. We briefly reviewed the relevance of each of these diseases, the drugs that have been used for treatment and those that are in development. Furthermore, we describe the rational design and synthesis strategies conducted by our research group, which have been focused on the development of new compounds with biological activity as potential anti-obesity, anti-cancer, anti-tuberculosis, and anti-trypanosomiasis agents.

En este artículo se describe de manera breve el trabajo que ha desarrollo nuestro grupo de investigación en el diseño, síntesis y evaluación biológica de moléculas con potencial terapéutico para problemas de salud pública tales como la obesidad, cáncer, tuberculosis y la tripanosomiasis americana o enfermedad de Chagas. Se realizó una revisión concisa de la relevancia de cada una de las enfermedades, los fármacos que se han usado para su tratamiento y aquellos que se han desarrollado recientemente. Además, se describen las estrategias de diseño racional y síntesis conducidas por nuestro grupo de investigación, las cuales se han enfocado en el desarrollo de nuevos compuestos con actividad biológica como potenciales agentes anti-obesidad, anti-cáncer, anti-tuberculosis y anti-tripanosomiasis.

We describe the synthesis of 12 new ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives on solid supports with room temperature and microwave-assisted solvent-free procedures. Results show that solid supports have good catalytic activity in the formation of quinoxaline 1,4-di-N-oxide derivatives. We found that florisil and montmorillonite KSF and K10 could be used as new, easily available, inexpensive alternatives of catalysts. Additionally, room temperature and microwave-irradiation solvent-free synthesis was more efficient than a conventional procedure (Beirut reaction), reducing reaction time and increasing yield.

In this work we report the synthesis of sulfonamide derivatives using a conventional procedure and with solid supports, such as silica gel, florisil, alumina, 4Å molecular sieves, montmorillonite KSF, and montmorillonite K10 using solvent-free and microwave-assisted methods. Our results show that solid supports have a catalytic activity in the formation of sulfonamide derivatives. We found that florisil, montmorillonite KSF, and K10 could be used as inexpensive alternative catalysts that are easily separated from the reaction media. Additionally, solvent-free and microwave-assisted methods were more efficient in reducing reaction time and in increasing yield.

The aims of this study were to formulate calcium-alginate beads containing glibenclamide, characterize the resulting microparticles, evaluate the release characteristics of this type of delivery system in an in vitro dissolution test, and compare it with two commercially available trademarks (Daonil® and Glibetab®). We obtained glibenclamide loaded calcium-alginate beads with a rough surface and a particle size between 150-200 µm. For the in vitro dissolution test Daonil® at 45 min showed a Q > 70%, whereas Glibetab® and glibenclamide calcium-alginate beads a Q < 70%; in spite of that glibenclamide calcium-alginate beads showed significant release properties.

We have developed an easy method for the synthesis of thirteen compounds derived from 1,2,4-triazoles through a carboxylic acid and hydrazinophthalazine reaction, with a 75-85% yield mediated by the use of agents such as 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride and 1-hydroxybenzotriazole. The operational simplicity of this method and the good yield of products make it valuable for the synthesis of new compounds with pharmacological activity.