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

On the feedback from super stellar clusters. I. The structure of giant HII regions and HII galaxies

We review the structural properties of giant extragalactic HII regions and HII galaxies based on 2D hydrodynamic calculations, and propose an evolutionary sequence that accounts for their observed detailed structure. The model assumes a massive and young stellar cluster surrounded by a large collection of clouds. These are thus exposed to the most important star-formation feedback mechanisms: photoionization and the cluster wind. The models show how the two feedback mechanisms compete in the disruption of clouds and lead to two different hydrodynamic solutions: The storage of clouds into a long lasting ragged shell that inhibits the expansion of the thermalized wind, and the steady filtering of the shocked wind gas through channels carved within the cloud stratum. Both solutions are claimed to be concurrently at work in giant HII regions and HII galaxies, causing their detailed inner structure. This includes multiple large-scale shells, filled with an X-ray emitting gas, that evolve to finally merge with each other, giving the appearance of shells within shells. The models also show how the inner filamentary structure of the giant superbubbles is largely enhanced with matter ablated from clouds and how cloud ablation proceeds within the original cloud stratum. The calculations point at the initial contrast density between the cloud and the intercloud media as the factor that defines which of the two feedback mechanisms becomes dominant throughout the evolution. Animated version of the models can be found at http://www.iaa.csic.es/\~{}eperez/ssc/ssc.html.Comment: 28 pages, 10 figures, accepted for publication in the ApJ. Animated version of the models can be found at http://www.iaa.csic.es/\~{}eperez/ssc/ssc.htm

The pressure confined wind of the massive and compact superstar cluster M82-A1

The observed parameters of the young superstar cluster M82-A1 and its associated compact HII region are here shown to indicate a low heating efficiency or immediate loss, through radiative cooling, of a large fraction of the energy inserted by stellar winds and supernovae during the early evolution of the cluster. This implies a bimodal hydrodynamic solution which leads to a reduced mass deposition rate into the ISM, with a much reduced outflow velocity. Furthermore, to match the observed parameters of the HII region associated to M82-A1, the resultant star cluster wind is here shown to ought to be confined by a high pressure interstellar medium. The cluster wind parameters, as well as the location of the reverse shock, its cooling length and the radius of the standing outer HII region are derived analytically. All of these properties are then confirmed with a semi-analytical integration of the flow equations, which provides us also with the run of the hydrodynamic variables as a function of radius. The impact of the results is discussed and extended to other massive and young superstar clusters surrounded by a compact HII region.Comment: 19 pages, 4 figures, accepted for publication in Ap

On the Extreme Positive Feedback Star-Forming Mode from Massive and Compact Superstar Clusters

The force of gravity acting within the volume occupied by young, compact and massive superstar clusters, is here shown to drive in situ all the matter deposited by winds and supernovae into several generations of star formation. These events are promoted by radiative cooling which drains the thermal energy of the ejected gas causing its accumulation to then rapidly exceed the gravitational instability criterion. A detailed account of the integrated ionizing radiation and mechanical luminosity as a function of time is here shown to lead to a new stationary solution. In this, the mass deposition rate $\dot M$, instead of causing a wind as in the adiabatic solution, turns into a positive feedback star-forming mode equal to the star formation rate. Some of the implications of this extreme positive feedback mode are discussed.Comment: 4 pages, 4 figures, accepted for publication in The Astrophysical Journal Letter

On the X-ray Emission from Massive Star Clusters and their Evolving Superbubbles

The X-ray emission properties from the hot thermalized plasma that results from the collisions of individual stellar winds and supernovae ejecta within rich and compact star clusters are discussed. We propose a simple analytical way of estimating the X-ray emission generated by super star clusters and derive an expression that indicates how this X-ray emission depends on the main cluster parameters. Our model predicts that the X-ray luminosity from the star cluster region is highly dependent on the star cluster wind terminal speed, a quantity related to the temperature of the thermalized ejecta.We have also compared the X-ray luminosity from the SSC plasma with the luminosity of the interstellar bubbles generated from the mechanical interaction of the high velocity star cluster winds with the ISM.We found that the hard (2.0 keV - 8.0 keV) X-ray emission is usually dominated by the hotter SSC plasma whereas the soft (0.3 keV - 2.0 keV) component is dominated by the bubble plasma. This implies that compact and massive star clusters should be detected as point-like hard X-ray sources embedded into extended regions of soft diffuse X-ray emission. We also compared our results with predictions from the population synthesis models that take into consideration binary systems and found that in the case of young,massive and compact super star clusters the X-ray emission from the thermalized star cluster plasma may be comparable or even larger than that expected from the HMXB population.Comment: 24 pages, 8 figures, Accepted for publication in The Astrophysical Journa

Revealing the obscured supernova remnant Kes 32 with Chandra

I report here on the analysis and interpretation of a Chandra observation of the supernova remnant Kes 32. Kes 32 is rather weak in X-rays due to a large interstellar absorption, which is found to be ~4E22 cm^-2, larger than previously reported. Spectral analysis indicates that the ionization age of this object is very young, with n_e t ~ 4E9 cm^-3s, and a temperature of kT_e ~ 1 keV. The X-ray emission peaks at a smaller radius than in the radio. The low ionization age suggests that Kes 32 is a young remnant. However, a young age is in contradiction with the relatively large apparent size, which indicates an age of several thousand years, instead of a few hundred years. This problem is discussed in connection with Kes 32's unknown distance and its possible association with the Norma galactic arm.Comment: Accepted for publication in the Astrophysical Journal. 7 pages, 7 figure

Two-Dimensional Hydrodynamic Models of Super Star Clusters with a Positive Star Formation Feedback

Using the hydrodynamic code ZEUS, we perform 2D simulations to determine the fate of the gas ejected by massive stars within super star clusters. It turns out that the outcome depends mainly on the mass and radius of the cluster. In the case of less massive clusters, a hot high velocity ($\sim 1000$ km s$^{-1}$) stationary wind develops and the metals injected by supernovae are dispersed to large distances from the cluster. On the other hand, the density of the thermalized ejecta within massive and compact clusters is sufficiently large as to immediately provoke the onset of thermal instabilities. These deplete, particularly in the central densest regions, the pressure and the pressure gradient required to establish a stationary wind, and instead the thermally unstable parcels of gas are rapidly compressed, by a plethora of re-pressurizing shocks, into compact high density condensations. Most of these are unable to leave the cluster volume and thus accumulate to eventually feed further generations of star formation. The simulations cover an important fraction of the parameter-space, which allows us to estimate the fraction of the reinserted gas which accumulates within the cluster and the fraction that leaves the cluster as a function of the cluster mechanical luminosity, the cluster size and heating efficiency.Comment: Accepted for publication in ApJ; 27 pages, 9 figures, 1 tabl

A Test of the Standard Hypothesis for the Origin of the HI Holes in Holmberg II

The nearby irregular galaxy Holmberg II has been extensively mapped in HI using the Very Large Array (VLA), revealing intricate structure in its interstellar gas component (Puche et al. 1992). An analysis of these structures shows the neutral gas to contain a number of expanding HI holes. The formation of the HI holes has been attributed to multiple supernova events occurring within wind-blown shells around young, massive star clusters, with as many as 10-200 supernovae required to produce many of the holes. From the sizes and expansion velocities of the holes, Puche et al. assigned ages of ~10^7 to 10^8 years. If the supernova scenario for the formation of the HI holes is correct, it implies the existence of star clusters with a substantial population of late-B, A and F main sequence stars at the centers of the holes. Many of these clusters should be detectable in deep ground-based CCD images of the galaxy. In order to test the supernova hypothesis for the formation of the HI holes, we have obtained and analyzed deep broad-band BVR and narrow-band H-alpha images of Ho II. We compare the optical and HI data and search for evidence of the expected star clusters in and around the HI holes. We also use the HI data to constrain models of the expected remnant stellar population. We show that in several of the holes the observed upper limits for the remnant cluster brightness are strongly inconsistent with the SNe hypothesis described in Puche et al. Moreover, many of the HI holes are located in regions of very low optical surface brightness which show no indication of recent star formation. Here we present our findings and explore possible alternative explanations for the existence of the HI holes in Ho II, including the suggestion that some of the holes were produced by Gamma-ray burst events.Comment: 30 pages, including 6 tables and 3 images. To appear in Astron. Journal (June 1999

Supergalactic winds driven by multiple superstar clusters

We present two dimensional hydrodynamic calculations of free expanding supergalactic winds, taking into consideration strong radiative cooling. Our main premise is that supergalactic winds are powered by collections of superstar clusters. Every individual superstar cluster is a source of a high metallicity radiative supersonic outflow (paper I, 2003, ApJ, 590, 791). The interaction of winds from neighboring knots of star formation is shown to lead to a collection of stationary oblique shocks and crossing shocks, able to structure the general outflow into a network of dense and cold, kpc long filaments that originate near the base of the outflow. The shocks also lead to extended regions of diffuse soft X-ray emission and furthermore, to channel the outflow with a high degree of collimation into the intergalactic medium.Comment: 10 pages, 5 figures, Accepted for publication in The Astrophysical Journa