Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7–9 and 17, were active against Leishmania parasites (EC50 = 9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25–27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.The authors thank COLCIENCIAS (contract No. 0333-2013, code: 111556933423) and the Universidad de Antioquia (Estrategia de Sostenibilidad 2013–2014 and CIDEPRO) for financial support

Synthesis and leishmanicidal activity of cinnamic acid esters: structure–activity relationship

Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 15–17, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 12–17); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 18–20 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.The authors thank Dr. Javier Garcés for his help in this study. We acknowledge the support by the Universidad de Antioquia (Estrategia de Sostenibilidad 2013–2014 and CIDEPRO) and Colciencias (contract No. 357-2011)

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a com- bination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis , which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against hu- man U-937 macrophages. Eight compounds were active against L. (V) panamensis ( 18 e 23, 26 and 30 ) and eight of them against T. cruzi ( 19 e 22 , 24 and 28 e 30 ) with EC 50 values lower than 40 m M. Compounds 19 e 22 , 24 and 28 e 30 showed higher activities than benznidazole (BNZ). Esters 19 and 21 were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82 and 11.65 m M and 8.25 and 8.69 m M, respectively. Compounds 19 e 22 , 24 and 28 e 30 showed higher activities than benznidazole (BNZ). Most of the compounds showed antiprotozoal activity and with exception of 18 , 26 and 28 , the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19 , bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity

Synthesis and Antiproliferative Activity of 3 and 7-Styrylcoumarins

A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c and 10d, exhibited the highest activity (IC50- SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity

Heavy Metal Tolerance of Microorganisms Isolated from Coastal Marine Sediments and Their Lead Removal Potential

In this study, 338 microorganisms, comprising 271 bacteria and 67 fungi, were isolated from sediment samples collected from underexplored Pacific and Caribbean regions of Colombia. Screening trials were conducted on selected strains (n = 276) to assess their tolerance to cadmium (Cd2+), lead (Pb2+), and zinc (Zn2+), leading to the identification of six bacteria capable of withstanding 750 mg·L−1 of each heavy metal ion. Three promising microorganisms, identified as Enterobacter sp. INV PRT213, Pseudomonas sp. INV PRT215, and Stenotrophomonas sp. INV PRT216 were selected for lead removal experiments using LB broth medium supplemented with 400 mg·L−1 Pb2+. Among these, Pseudomonas sp. INV PRT215 exhibited significant potential, removing 49% of initial Pb2+ after 240 min of exposure (16.7 g wet biomass·L−1, pH 5, 30 °C). Infrared spectra of Pb-exposed biomass showed changes in functional groups, including carbonyl groups of amides, carboxylate, phosphate, hydroxyl, and amine groups, compared to the not-exposed control. These changes suggested interactions between the metal and functional groups in the biomass. The findings of this study highlight the potential of microorganisms derived from coastal marine environments as promising candidates for future applications in bioremediation of polluted environments contaminated with heavy metals

Manual del modelo de gestión de la cultura y capacidad de innovación empresarial – CCIE: Una oportunidad para innovar y mejorar el valor diferenciador en las microempresas.

Encontraras el libro completo.La relación empresa-universidad ha cobrado vital importancia en los últimos años. Cada vez más, economías robustas principalmente europeas, se han beneficiado de la aplicación óptima de este tipo de colaboración. Desde el contexto universitario, se busca analizar tendencias y hacer más ágiles las respuestas académicas a las necesidades del entorno. Desde el contexto empresarial, existe la presión de la mejora continua de sus conocimientos y tecnologías, que aseguren su existencia en el largo plazo. Es así como las universidades se convierten en una fuente de investigación alternativa para lo que antes se desarrollaba internamente en las organizaciones y que hoy, por diversos motivos, entre esos el avance tecnológico a pasos agigantados, hace que estas miren a la academia, ya no solo como un formador de profesionales sino como un socio estratégico

Manual del modelo de gestión de la cultura y capacidad de innovación empresarial – CCIE: Una oportunidad para innovar y mejorar el valor diferenciador en las microempresas.

Encontraras el libro completo.La relación empresa-universidad ha cobrado vital importancia en los últimos años. Cada vez más, economías robustas principalmente europeas, se han beneficiado de la aplicación óptima de este tipo de colaboración. Desde el contexto universitario, se busca analizar tendencias y hacer más ágiles las respuestas académicas a las necesidades del entorno. Desde el contexto empresarial, existe la presión de la mejora continua de sus conocimientos y tecnologías, que aseguren su existencia en el largo plazo. Es así como las universidades se convierten en una fuente de investigación alternativa para lo que antes se desarrollaba internamente en las organizaciones y que hoy, por diversos motivos, entre esos el avance tecnológico a pasos agigantados, hace que estas miren a la academia, ya no solo como un formador de profesionales sino como un socio estratégico

<i>Sargassum filipendula</i>, a Source of Bioactive Compounds with Antioxidant and Matrix Metalloproteinases Inhibition Activities In Vitro with Potential Dermocosmetic Application

The antioxidant and the potential inhibitory capacity of matrix metalloproteinases of the phlorotannin-type polyphenolic and fucoidan-type polysaccharides extracts obtained from the macroalga S. filipendula were evaluated. Through chromatographic and spectroscopic techniques, the corresponding chemical structure of compounds present in the extracts was determined. Antioxidant capacity was evaluated using the methyl linoleate model for the inhibition of lipid peroxidation, and the free radical scavenging capacity was assessed using DPPH, ABTS, •OH, O2•− methods. The matrix metalloproteinase inhibition potential was measured by collagenase and elastase inhibition tests, using epigallocatechin gallate as a positive control. The extracts exhibited a high scavenging capacity of radical species evaluated and inhibition of diene conjugate formation and thiobarbituric acid reactive substances. The results showed that the crude extracts presented dose-dependent collagenase and elastase inhibition, with IC50 values between 0.04 and 1.61 mg/mL. The structure of the residues of the polysaccharide was identified mainly as (1→3)-sulfated (1→3) α-l-fucopyranose at carbon 4 and residues of β-d-glucopyranose, α-d-Mannopyranose, and β-d-Galactopyranose, while in the polyphenol extract the presence of phloroglucinol was identified and the presence of eckol, bifuhalol, and trifuhalol was suggested. Our results allow us to infer that S. filipendula is a potential source of bioactive ingredients with antioxidant and anti-aging activity

Synthesis and antiprotozoal activity of furanchalcone–quinoline, furanchalcone–chromone and furanchalcone–imidazole hybrids

We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of several furanchalcone–quinoline, furanchalcone–chromone, and furanchalcone–imidazole hybrids. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia and against Trypanosoma cruzi, which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds (6e, 8a–8f, 11b, and 11c) were active against both L. (V) panamensis and T. cruzi being 8e and 8f the most active compounds with an EC50 of 0.78 and 2.16 µM against L. (V) panamensis, respectively, and 0.66 and 0.72 µM against T. cruzi, respectively. Seven hybrid compounds showed better activity than meglumine antimoniate and the anti-trypanosomal activity of nine compounds were higher than benznidazole. Although these compounds showed toxicity for mammalian U-937 cells, they still have the potential to be considered as candidates for antileishmanial or trypanocydal drug development. There is not a clear relationship between the antiprotozoal activity and the length of the alkyl linker. However, we obtained higher bioactivity when the alkyl linker has nine and twelve carbon atoms. Furanchalcone-imidazole hybrids were the most active of all compounds, showing that the imidazole salt moiety is important for their biological actions