Pharmacophore modeling, 3D-QSAR,docking, and molecular dynamics simulation on topoisomerase IV inhibitors of wild type Staphylococcus aureus

Staphylococcus aureus is a gram-positive bacterium. It is a foremost cause of skin and respiratory infections, endocarditis, osteomyelitis, Ritter’s disease, and bacteraemia. Topoisomerase enzyme is involved in preventing or correcting topological problems of overwinding or underwinding occurring in DNA before replication process. An exhaustive molecular modeling studies that includes pharmacophore modeling, ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics simulation, and ADME calculations were performed on isothiazoloquinolones derivatives which are reported as effective inhibitors against topoisomerase IV of wild type S. aureus. In pharmacophore modeling by using pharmacophore alignment and scoring engine (PHASE) a five-point model (AHHRR.3) was generated with existing compounds having statistical significant as correlation coefficient (R ² = 0.954), cross-validation coefficient (Q ² = 0.650), and F value of 130.5. Ligand-based 3D-QSAR study was applied using comparative molecular field analysis (CoMFA) with Q ² = 0.616, R ² = 0.989, and comparative molecular similarity indices analysis (CoMSIA) with Q ² = 0.510, R ² = 0.995. The predictive ability of this model was determined using a test set of molecules that gave acceptable predictive correlation (R ² Pred) values 0.55 and 0.56 for CoMFA and CoMSIA, respectively. Docking and molecular dynamic simulations were employed to position the inhibitors into protein active site to find out the most probable binding mode and most reliable conformations. Developed pharmacophore models and docking methods provide guidance to design enhanced activity molecules.

     

Clifford Fourier Transformation and Uncertainty Principle for the Clifford Geometric Algebra Cl 3,0

First, the basic concept of the vector derivative in geometric algebra is introduced. Second, beginning with the Fourier transform on a scalar function we generalize to a real Fourier transform on Clifford multivector-valued functions Third, we show a set of important properties of the Clifford Fourier transform on Cl_3,0 such as differentiation properties, and the Plancherel theorem. Finally, we apply the Clifford Fourier transform properties for proving an uncertainty principle for Cl_3,0 multivector functions.     

A lattice Boltzmann model for coupled diffusion

Diffusion coupling between different chemical components can have significant effects on the distribution of chemical species and can affect the physico-chemical properties of their supporting medium. The coupling can arise from local electric charge conservation for ions or from bound components forming compounds. We present a new lattice Boltzmann model to account for the diffusive coupling between different chemical species. In this model each coupling is added as an extra relaxation term in the collision operator. The model is tested on a simple diffusion problem with two coupled components and is in excellent agreement with the results obtained through a finite difference method. Our model is observed to be numerically very stable and unconditional stability is shown for a class of diffusion matrices. We further develop the model to account for advection and show an example of application to flow in porous media in two dimensions and an example of convection due to salinity differences. We show that our model with advection loses the unconditional stability, but offers a straight-forward approach to complicated two-dimensional advection and coupled diffusion problems.     

Synthesis,Spectral Characterization,DNA/ Protein Binding,DNA Cleavage,Cytotoxicity, Antioxidative and Molecular Docking Studies of Cu(II)Complexes Containing Schiff Base-bpy/Phen Ligands

Ternary Cu(II) complexes [Cu(II)(L)(bpy)Cl] 1, [Cu(II)(L)(Phen)Cl] 2 [L = 2,3–dimethyl-1-phenyl-4(2 hydroxy-5-methyl benzylideneamino)-pyrazol-5-one, bpy = 2,2^′ bipyridine, phen =1,10 phenanthroline) were synthesized and characterized by elemental analyses, UV-Visible, FT-IR, ESR, Mass, thermogravimetric and SEM EDAX techniques. The complexes exhibit octahedral geometry. The interaction of the Cu(II) with cailf thymus DNA (CT-DNA) was explored by using absorption and fluorescence spectroscopic methods. The results revealed that the complexes have an affinity constant for DNA in the order of 10⁴ M^?1 and mode of interaction is intercalative mode. The DNA cleavage study showed that the complexes cleaved DNA without any external agent. The interaction of Cu(II) complexes with bovine serum albumin (BSA) was also studied using absorption and fluorescence techniques. The cytotoxic activity of the Cu(II) complexes was probed in HeLa (human breast adenocarcinoma cell line), B16F10 (Murine melanoma cell line) and HEPA1–6 celllines, complex 1 has good cytotoxic activity which is comparable with the doxarubicin drug, with IC₅₀ values ranging from 3 to 12.6 μM. A further molecular docking technique was employed to understand the binding of the complexes towards the molecular target DNA. Investigation of the antioxidative properties showed that the metal complexes have significant radical scavenging activity potency against DPPH radical.     

Fabrication of visible light driven nano structured Copper,Boron codoped TiO2 for photocatalytic removal of Lissamine Green B

In the present research work a potentially improved Copper (Cu) and Boron (B) codoped TiO₂ nano materials were synthesized by varying the different dopant concentrations (Copper 0.25, 0.50, 0.75, 1?wt% and Boron 0.25, 0.50, 0.75, 1?wt%) using solgel method for the photocatalytic degradation of Lissamine Green B. In order to investigate the physical, chemical and optical properties of a catalyst, which play a key role in its photocatalytic activity, as prepared samples were characterized by various instrumental techniques. The crystalline phase study performed for all the samples using X-ray powder diffraction (XRD) confirmed the formation of anatase TiO₂. Chemical composition of the prepared catalyst investigated by X-ray photo electron spectroscopy (XPS) affirmed the presence of constituent elements (Ti, O, Cu & B) on the catalyst surface. The surface microstructure studied by field emission scanning electron microscopy (FE-SEM) revealed that the TiO₂ particles having spherical shape with rough surface morphology. The average particle size and surface area of the catalyst determined by high-resolution transmission electron microscopy (HRTEM) and Brunauer-Emmett-Teller (BET) surface area analyser, revealed that the codoped catalyst shows a high percentage of small particles of size 6.8?nm and a high surface area of 135.6?m²/g, respectively. The band edge absorption shift of the samples was determined by diffuse reflectance spectroscopy analysis (DRS) and the results exhibited that among all the codoped samples Copper 0.25?wt% and Boron 1?wt% (CBT1) catalyst shows a reduced band gap energy of 2.73?eV. The characterization results supported the photocatalytic activity of the catalyst for the degradation of Lissamine Green B within 90?min at the optimum reaction parameters such as dopant concentration of Cu at 0.25?wt% & B at 1?wt%, pH?=?3, catalyst dosage 0.075?g/L and dye concentration 10?mg/L under visible light irradiation. The mechanism of enhanced photocatalytic performance of the catalyst was proposed by the results obtained from the PL spectra and main reactive species trapping measurements.     

Single quantum dot spontaneous emission in a finite-size photonic crystal waveguide: proposal for an efficient "on chip" single photon gun

Spontaneous emission rate enhancements from a single quantum dot embedded in a finite-size, planar photonic-crystal waveguide are investigated. Short waveguide lengths of only 10 to 20 unit cells are found to produce very large Purcell factors associated with a waveguidelike sharp resonance feature in the local density of photon states. Aided by theoretical insight and rigorous computational calculations, we explain the physics behind these remarkable emission enhancements and subsequently propose a "single-photon gun" with on-chip unidirectional collection efficiencies greater than 60% into an output wire waveguide. The advantages over recent proposals for infinitely long photonic-crystal waveguides are highlighted.     

Design and synthesis of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-diones: a potential cytotoxic scaffolds and their molecular modeling studies

In an effort to discover potential cytotoxic agents, a series of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-dione derivatives (8a–n) were designed and synthesized in various steps with acceptable reaction procedures with quantitative yields and characterized by ¹H NMR, ¹³C NMR, IR, HRMS and ESI–MS spectra. These newly synthesized novel derivatives were screened for their in vitro cell viability/cytotoxic studies against human breast cancer cell line (MCF-7) with various concentrations of 0.625 µM, 1.25 µM, 2.5 µM, 5 µM and 10 µM, respectively. The biological interpretation assay outcome was demonstrated in terms of cell viability percentage reduction and IC₅₀ values against standard reference drug cisplatin. Based on these results, most of the derivatives exhibited promising cytotoxic activity. Among them, particularly compounds 8j (R₁?=?OMe and R₃?=?NO₂) and 8e (R₃?=?CF₃) demonstrate remarkable cytotoxic activity with IC₅₀ values 0.426 µM?±?0.455 and 0.608 µM?±?0.408, which are even better than the standard drug cisplatin 0.636 µM?±?0.458 and compounds 8m (R₂?=?OMe and R₃?=?OMe) and 8c (R₃?=?OMe) exhibited closely equivalent IC₅₀ values to the standard drug with IC₅₀ values 0.95 µM?±?0.32 and 0.976 µM?±?0.313 and rest of the compounds exhibits moderate cytotoxic activity. Moreover, molecular modeling studies and ADME calculations of the novel synthesized derivatives are in adequate consent with the pharmacological screening results.