In Silico Prediction,Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECD_GC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECD_GC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECD_GC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECD_GC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.     

Method of Generating N-dimensional Isochronous Nonsingular Hamiltonian Systems

In this paper we develop a straightforward procedure to construct higher dimensional isochronous Hamiltonian systems. We first show that a class of singular Hamiltonian systems obtained through the Ω-modified procedure is equivalent to constrained Newtonian systems. Even though such systems admit isochronous oscillations, they are effectively one degree of freedom systems due to the constraints. Then we generalize the procedure in terms of Ω _i -modified Hamiltonians and identify suitable canonically conjugate coordinates such that the constructed Ω _i -modified Hamiltonian is nonsingular and the corresponding Newton's equation of motion is constraint free. The procedure is first illustrated for two dimensional systems and subsequently extended to N-dimensional systems. The general solution of these systems are obtained by integrating the underlying equations and is shown to admit isochronous as well as amplitude independent quasiperiodic solutions depending on the choice of parameters.     

Synthesis,Characterization, and in vitro Antibacterial Evaluation of Barbituric Acid Derivatives

Russian Journal of Organic Chemistry - A series of 5,5′-(arylmethylene)bis[1,3-dimethyl-6-(methylamino)pyrimidine-2,4(1H,3H)-diones] have been synthesized by 2: 1 condensation of...     

CuSO4/sodium ascorbate catalysed synthesis of benzosuberone and 1,2,3-triazole conjugates: Design,synthesis and in vitro anti-proliferative activity

A novel series of conjugates of benzosuberone and 1,2,3-triazole i.e. 3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl-9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulene-8-carboxylic acids (8a-j) were synthesized in good to excellent yields catalysed by CuSO₄ under milder reaction conditions and evaluated for their anti-proliferative activity. The structural elucidation of the prepared compounds was carried out using IR, ¹H NMR, ¹³C NMR and Mass spectral analysis. The newly synthesized derivatives (8a-j) were evaluated for their anti-proliferative activity against four human cell lines and the novel derivatives showed moderate to excellent activity. The obtained results suggest that these compounds can be considered as new hits for anti-proliferative drug development programme and further SAR studies can help obtain better anticancer agents.     

Spectroscopic database of CO2 line parameters: 4300-7000 cm

A new spectroscopic database for carbon dioxide in the near infrared is presented to support remote sensing of the terrestrial planets (Mars, Venus and the Earth). The compilation contains over 28,500 transitions of 210 bands from 4300 to 7000 cm⁻¹ and involves nine isotopologues: ¹⁶O¹²C¹⁶O (626), ¹⁶O¹³C¹⁶O (636), ¹⁶O¹²C¹⁸O (628), ¹⁶O¹²C¹⁷O (627), ¹⁶O¹³C¹⁸O (638), ¹⁶O¹³C¹⁷O (637), ¹⁸O¹²C¹⁸O (828), ¹⁷O¹²C¹⁸O (728) and ¹⁸O¹³C¹⁸O (838). Calculated line positions, line intensities, Lorentz half-width and pressure-induced shift coefficients for self- and air-broadening are taken from our recent measurements and are presented for the Voigt molecular line shape. The database includes line intensities for 108 bands measured using the McMath-Pierce Fourier transform spectrometer located on Kitt Peak, Arizona. The available broadening parameters (half-widths and pressure-induced shifts) of ¹⁶O¹²C¹⁶O are applied to all isotopologues. Broadening coefficients are computed using empirical expressions that have been fitted to the experimental data. There are limited data for the temperature dependence of widths and so no improvement has been made for those parameters. The line intensities included in the catalog vary from 4×10⁻³⁰ to 1.29×10⁻²¹ cm⁻¹/(molecule cm⁻²) at 296 K. The total integrated intensity for this spectral interval is 5.9559×10⁻²⁰ cm⁻¹/(molecule cm⁻²) at 296 K.     

Switchable ErSc2N rotor within a C80 fullerene cage: an electron paramagnetic resonance and photoluminescence excitation study

Motivated by the possibility of observing photoluminescence and electron paramagnetic resonance from the same species located within a fullerene molecule, we initiated an EPR study of Er3+ in ErSc2N@C80. Two orientations of the ErSc2N rotor within the C80 fullerene are observed in EPR, consistent with earlier studies using photoluminescence excitation (PLE) spectroscopy. For some crystal field orientations, electron spin relaxation is driven by an Orbach process via the first excited electronic state of the 4I(15/2) multiplet. We observe a change in the relative populations of the two ErSc2N configurations upon the application of 532 nm illumination, and are thus able to switch the majority cage symmetry. This photoisomerization, observable by both EPR and PLE, is metastable, lasting many hours at 20 K.     

Effect of cation doping on low-temperature specific heat of LaMnO3 manganite

We have investigated the thermodynamic properties of perovskite manganite LaMnO₃, the parent compound of colossal magnetoresistive manganites, with the Ca²⁺ doping at the A-site. As strong electron-phonon interactions are present in these compounds, the lattice part of the specific heat deserves proper attention. We have described the temperature dependence of the lattice contribution to the specific heat at constant volume (C_v(lattice)) of La_1−xCa_xMnO₃ (x=0.125, 0.175, 0.25, 0.35, 0.50, 0.67, 0.75) as a function of temperature (1 K–20 K) by means of a rigid ion model (RIM).The trends of specific heat variations with temperature are almost similar at all the composition. The Debye temperatures obtained from the lattice contributions are found to be in somewhat closer agreement with the experimental data. The specific heat values revealed by using RIM are in closer agreement with the available experimental data, particularly at low temperatures for some concentrations (x) of La_1−xCa_xMnO₃. The theoretical results at higher temperatures can be improved by including the effects of the charge ordering, van der Waals attraction and anharmonicity in the framework of RIM.     

Ab initio calculation of vibrational frequencies of GexSe1−x glass

We have used the density functional theory to make the models of Ge_xSe_1?x glass for which the energy is a minimum. The clusters, Ge₂Se₂, Ge₂Se₃, Ge₃Se, Ge₃Se₂, Ge₄Se, GeSe₃, GeSe₄, chain mode zig-zag Ge₄Se₃, corner sharing GeSe₄, and edge sharing Ge₂Se₆, have been made successfully and their vibrational spectra have been calculated from the first principles. We are able to optimize the bond distances as well as the bond angles. The calculated values of the frequencies of vibrations of the various clusters have been compared with those obtained from the experimental Raman spectra of actual glasses, Ge_xSe_1?x(0 < x < 0.3). The local concentration, x within 0.25 nm is nonuniform in the amorphous material. When the same cluster occurs in two stable configurations, low frequency vibrations of frequency, ν < 100 cm^?1, are found. The corner sharing GeSe₄ has low frequency modes at 54 cm^?1 and 93 cm^?1 whereas these modes disappear in the pyramidal configuration. The low frequency modes are therefore associated with the breaking of C₄ symmetry of the pyramidal configuration. The computed vibrational frequencies of clusters Ge₃, Ge₄Se₃, Ge₂Se₃, GeSe₃ and Ge₃Se₂ are actually present in the Raman spectra of the glass, Ge_xSe_1?x(0 < x < 0.3).     

Influence of Cross-Sectional Uncertainty on Sensitivity Studies of DUNE and T2HK Experiments

International Journal of Theoretical Physics - We successfully realized symmetric and asymmetric cyclic quantum teleportation by using different controllers for each receiver. In this study, Alice...