Estudios de acoplamiento molecular de nuevos análogos de quinolonas a la ADN girasa de Escherichia coli

Indexación: Scopus.Chemicals and CAS Registry Numbers: amino acid, 65072-01-7; ciprofloxacin, 85721-33-1; DNA topoisomerase (ATP hydrolysing); gatifloxacin, 112811-59-3, 180200-66-2; levofloxacin, 100986-85-4, 138199-71-0; lomefloxacin, 98079-51-7; moxifloxacin, 151096-09-2; nalidixic acid, 389-08-2; oxolinic acid, 14698-29-4; pipemidic acid, 51940-44-4; rufloxacin, 101363-10-4; sitafloxacin, 127254-12-0, 163253-35-8Context: Bacterial resistance to antibiotics is the inevitable consequence of the use of antimicrobial agents. Thus, quinolones are an important class of antibacterials; these agents generally consist of a 1-subtituted-1,4-dihydro-4-oxopyridine-3-carboxylic acid moiety combined with an aromatic or heteroaromatic ring fused at the 5- and 6-position. Aims: To determine the binding of quinolones to DNA gyrase of Escherichia coli. Methods: An analysis was performed using an in silico approach to determine, by docking calculations and energy descriptors, the conformer of 4‐oxo‐1,4‐dihydroquinoline skeleton that forms the most stable complex with DNA gyrase of E. coli. Results: The complex shows that the pose of the quinolones coincides with the amino acid residues Asp87, Thr88, Arg91 and Met92, which is expected to be critical in the binding of quinolones to DNA gyrase of E. coli. A series of quinolones were computationally designed, and the interactions between the quinolones and the amino acid residues of the DNA gyrase were calculated. Conclusions: Among the designed compounds, compounds 105 and 115 exhibit higher binding energy values and interact with amino acids Asp87, Thr88, Arg91 and Met92. © 2018 Journal of Pharmacy & Pharmacognosy Research.http://jppres.com/jppres/pdf/vol6/jppres18.368_6.5.386.pd

NEW PHOSPHORUS COMPOUNDS K[PCL3(X)] (X= SCN, CN): PREPARATION AND DFT AND SPECTROSCOPIC STUDIES

Indexación: Web of Science. Scielo.Two new phosphorus complexes, potassium trichlorothiocyanophosphate (III) (PTCTCP; K[PCl3(SCN)]) and potassium trichlorocyanophosphate (III) (PTCCP; K[PCl3(CN)]) were synthesized from the reaction of KSCN and KCN, respectively, with PC^. The chemical formulas and compositions of these compounds were determined by elemental analysis and spectroscopic methods, such as phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy (31P-NMR), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy and mass spectrophotometry. All of the theoretical calculations and determinations of the properties of these compounds were performed as part of the Amsterdam Density Functional (ADF) program. Excitation energies were assessed using time-dependent perturbation density functional theory (TD-DFT). In addition, the molecular geometry was optimized and the frequencies and excitation energies were calculated using standard Slater-type orbital (STO) basis sets with triple-zeta quality double plus polarization functions (TZ2P) for all of the atoms. The assignment of the principal transitions and total densities of state (TDOS) for orbital analysis were performed using the GaussSum 2.2 program.http://www.scielo.cl/pdf/jcchems/v61n1/art15.pd

Docking studies on novel analogs of quinolones against DNA gyrase of Escherichia coli

Context: Bacterial resistance to antibiotics is the inevitable consequence of the use of antimicrobial agents. Thus, quinolones are an important class of antibacterials; these agents generally consist of a 1-subtituted-1,4-dihydro-4-oxopyridine-3-carboxylic acid moiety combined with an aromatic or heteroaromatic ring fused at the 5- and 6-position. Aims: To determine the binding of quinolones to DNA gyrase of Escherichia coli. Methods: An analysis was performed using an in silico approach to determine, by docking calculations and energy descriptors, the conformer of 4‐oxo‐1,4‐dihydroquinoline skeleton that forms the most stable complex with DNA gyrase of E. coli. Results: The complex shows that the pose of the quinolones coincides with the amino acid residues Asp87, Thr88, Arg91 and Met92, which is expected to be critical in the binding of quinolones to DNA gyrase of E. coli. A series of quinolones were computationally designed, and the interactions between the quinolones and the amino acid residues of the DNA gyrase were calculated. Conclusions: Among the designed compounds, compounds 105 and 115 exhibit higher binding energy values and interact with amino acids Asp87, Thr88, Arg91 and Met92

Relationships between the structural characteristic of curcumins that affect cell proliferation of hepatocarcinoma cells

Relationships between the structural characteristic of curcumin and dimethoxycurcumin and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with the curcumin and dimethoxycurcumin resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated docking and the DFT method, suggest a structure-activity relationship between the activities of dimethoxycurcumin and curcumin structure and the apoptosis in HepG2 cell

A Multiwavelength View of a Mass Outflow from the Galactic Center

The Galactic center (GC) lobe is a degree-tall shell of gas that spans the central degree of our Galaxy. It has been cited as evidence for a mass outflow from our GC region, which has inspired diverse models for its origin. However, most work has focused on the morphology of the GC lobe, which has made it difficult to draw strong conclusions about its nature. Here, I present a coherent, multiwavelength analysis of new and archival observations of the GC lobe. Radio continuum emission shows that the GC lobe has a magnetized layer with a diameter of 110 pc and an equipartition field strength ranging from 40 to 100 $\mu$G. Recombination line emission traces an ionized shell nested within the radio continuum with diameter of 80 pc and height 165 pc. Mid-infrared maps at 8 and 15 $\mu$m show that the GC lobe has a third layer of warm dust and PAH-emission that surrounds the radio continuum shell with a diameter of 130 pc. Assuming adiabatic expansion of the gas in the GC lobe, its formation required an energy input of about $5\times10^{52}$ ergs. I compare the physical conditions of the GC lobe to several models and find best agreement with the canonical starburst outflow model. The formation of the GC lobe is consistent with the currently observed pressure and star formation rate in the central tens of parsecs of our Galaxy. Outflows of this scale are more typical of dwarf galaxies and would not be easily detected in nearby spiral galaxies. Thus, the existence of such an outflow in our own Galaxy may indicate that it is relatively common phenomenon in the nuclei of spiral galaxies. (Abridged)Comment: Accepted to ApJ. 15 pages, 8 (compressed) figure

Octahedral molybdenum cluster complexes with aromatic sulfonate ligands

This article describes the synthesis, structures and systematic study of the spectroscopic and redox properties of a series of octahedral molybdenum metal cluster complexes with aromatic sulfonate ligands (nBu4N)2[{Mo6X8}(OTs)6] and (nBu4N)2[{Mo6X8}(PhSO3)6] (where X- is Cl-, Br- or I-; OTs- is p-toluenesulfonate and PhSO3 - is benzenesulfonate). All the complexes demonstrated photoluminescence in the red region and an ability to generate singlet oxygen. Notably, the highest quantum yields (>0.6) and narrowest emission bands were found for complexes with a {Mo6I8}4+ cluster core. Moreover, cyclic voltammetric studies revealed that (nBu4N)2[{Mo6X8}(OTs)6] and (nBu4N)2[{Mo6X8}(PhSO3)6] confer enhanced stability towards electrochemical oxidation relative to corresponding starting complexes (nBu4N)2[{Mo6X8}X6]

Structural Antitumoral Activity Relationships of Synthetic Chalcones

Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series

One-pot synthesis of {Mo6 I8 }4+ -doped polystyrene microspheres via a free radical dispersion copolymerisation reaction:{Mo6 I8 }4+ -doped polystyrene microspheres via free radical copolymerisation

Molybdenum octahedral clusters, when incorporated into an appropriate polymer matrix, are considered as promising agents for a range of biological applications. This work describes the one-pot synthesis, morphology and cellular toxicity of nano-sized polystyrene beads doped with luminescent cluster complexes [(Mo6X8)(NO3)6]2- (X=Cl, Br or I). Specifically, the particles were obtained by free radical dispersion copolymerisation of styrene and methacrylic acid or 4-vinylpyridine in the presence of the cluster complexes. The effects of the cluster loading in the reaction mixture on both the content of the final material and number-average molar mass of the copolymers were evaluated

Effects of Galactic fountains and delayed mixing in the chemical evolution of the Milky Way

The majority of galactic chemical evolution models assumes the instantaneous mixing approximation (IMA). This assumption is probably not realistic as indicated by the existence of chemical inhomogeneities, although current chemical evolution models of the Milky Way can reproduce the majority of the observational constraints under the IMA. The aim of this paper is to test whether relaxing this approximation in a detailed chemical evolution model can improve or worsen the agreement with observations. To do that, we investigated two possible causes for relaxing of the instantaneous mixing: i) the ``galactic fountain time delay effect'' and ii) the ``metal cooling time delay effect''. We found that the effect of galactic fountains is negligible if an average time delay of 0.1 Gyr, as suggested in a previous paper, is assumed. Longer time delays produce differences in the results but they are not realistic. We also found that the O abundance gradient in the disk is not affected by galactic fountains. The metal cooling time delays produce strong effects on the evolution of the chemical abundances only if we adopt stellar yields depending on metallicity. If instead, the yields computed for to the solar chemical composition are adopted, negligible effects are produced, as in the case of the galactic fountain delay. The relaxation of the IMA by means of the galactic fountain model, where the delay is considered only for massive stars and only in the disk, does not affect the chemical evolution results. The combination of metal dependent yields and time delay in the chemical enrichment from all stars starting from the halo phase, instead, produces results at variance with observations.Comment: Accepted by A&

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

<p>Abstract</p> <p>Background</p> <p>Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods.</p> <p>Results</p> <p>Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values.</p> <p>Conclusions</p> <p>Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.</p