Biomedical subjects

Aneta Jezierska

Publications and source records attributed to Aneta Jezierska.

9 recordsLinked to original sources

PubMed2004

Density functional calculation of the 2D potential surface and deuterium isotope effect on 13C chemical shifts in picolinic acid N-oxide. Comparison with experiment.

2D free energy surfaces V = V(rOH, rO...O) for the intramolecular H-bond in the title compound were calculated by the DFT method and used in the calculation of primary and secondary chemical shifts of the compound dissolved in chloroform and acetonitrile. Solvent effects were accounted for by the SCRF/PCM method. The corresponding two-dimensional chemical shift surfaces with included solvent reaction field were obtained using the Continuous Set of Gauge Transformations approach at the B3LYP/6-311+G(2d,2p) level of theory. The chemical shifts were estimated as quantum averages along the two internal coordinates in the hydrogen bond and along several vibrational levels according to the Boltzmann distribution at room temperature. Fairly good agreement between the experimental and calculated isotope effects was obtained. 1D and 2D NMR spectra of solutions of picolinic acid N-oxide and its deuterated analogue were recorded and assigned.

Journal Article↗

PubMed2004

Structure/activity investigations of 5-substituted 3-methylisoxazole[5, 4-d]1, 2, 3-triazin-4-one derivatives.

The series of 5-substituted 3-methylisoxazole[5, 4-d]1, 2, 3-triazin-4-one derivatives was obtained by diazotization of 5-amino-3-methylisoxazol-4-carboxylic acid hydrazide. The immunological activity of these compounds was investigated experimentally in several in vitro and in vivo assays in mice and human models. In the next step, quantum-chemical investigations were performed using density functional theory with the B3LYP hybrid exchange-correlation energy functional and 6-31G(d, p) basis set. The Polarizable Continuum (SCRF/PCM) solvent model was also taken into account in order to show solvent influence on electron density and electrostatic potential around the exemplary molecules. Correlations between molecular structure and biological properties were found using a stepwise selection of scales for the multiple linear regression (MLR).

Animals↗

PubMed2004

Counter-propagation artificial neural network as a tool for the independent variable selection: structure-mutagenicity study on aromatic amines.

The counter-propagation artificial neural network (CP ANN) technique was applied for the independent variable selection and for structure-mutagenic potency modeling on a set of 95 aromatic and heteroaromatic amines with biological activity investigated experimentally by an in vitro assay. The molecular structures were represented by 275 independent variables classified as topostructural, topochemical, geometrical and quantum-chemical descriptors. As a result of the neural network modeling, the following descriptors were found to be the most important for structure-activity relationship: 5 chi -path connectivity index of order h = 5, 3chibC-bond cluster connectivity index of order h = 3, J(B)-Balaban's J index based on bond types, SHSNH2-electrotopological state index values for atoms, phia-flexibility index (kappa p1 x kappa p2/nvx), IC0-mean information content or complexity of a graph based on the 0 order neighborhood of vertices in a hydrogen-filled graph and ELUMO. The leave one out (LOO) method was used in order to test and select the models for mutagenicity prediction. The statistical parameters for the 7-descriptors model are R(Model) = 0.96 and Rcv = 0.85, respectively. In the next step, the number of variables was reduced and the 4-descriptors model was found (R(Model) = 0.95 and Rcv = 0.85) and classified as the best one.

Algorithms↗

PubMed2003

An experimental and theoretical structural study of 5-amino-3-methylisoxazolo-4-carboxylic acid p-chlorophenylamide.

Experimental and theoretical structural studies of 5-amino-3-methylisoxazolo-4-carboxylic acid p-chlorophenylamide were performed. This compound belongs to a new class of isoxazole derivatives exhibiting promising immunological activity. The crystallographic structure was measured and compared with theoretical calculations for the investigated compound. The theoretical analyses were performed using Kohn-Sham density functional theory (DFT) with the B3LYP hybrid exchange-correlation energy functional and 6-311+G(d,p) basis set. The solvent effect was included using the SCRF/PCM method with water (epsilon=78) as a solvent. Topological analysis was performed in terms of Bader's theory of atoms in molecules, yielding molecular parameters for quantum molecular similarity investigations. Figure The SCRF/PCM map of electrostatic potential around the molecule: light grey isosurface at +0.5 a.u., dark grey at -0.05 a.u.

Computer Simulation↗

PubMedDate not supplied

Modeling toxicity by using supervised kohonen neural networks.

Counterprogation neural network is shown to be a powerful and suitable tool for the investigation of toxicity. This study mined a data set of 568 chemicals. Two hundred eighty-two objects were used as the training set and 286 as the test set. The final model developed presents high performances on the data set R(2) = 0.83 (R(2) = 0.97 on the training set, R(2) = 0.59 on the test set). This technique distinguishes itself also for the ability to give to the expert two-dimensional maps suitable for the study of the distribution/clustering of the data and the identification of outliers.

Journal Article↗

PubMedDate not supplied

Kohonen network study of aromatic compounds based on electronic and nonelectronic structure descriptors.

Atoms in Molecules (AIM) and Electron Localization Function (ELF) methodologies were applied to describe the electronic structure of 88 aromatic compounds. The analyzed database contains molecules substituted by nucleophilic and electrophilic groups which are responsible for electron density distribution in the molecule and further for its reactivity. Radial Distribution Function (RDF), Weighted Holistic Invariant Molecular (WHIM), Three-Dimensional Molecule Representation of Structures based on Electron Diffraction (3D-MoRSE) and Geometry, Topology and Atom-Weights Assembly (GETAWAY) descriptors were taken into account describing the structures of the analyzed molecules. According to generated descriptor space the classification of the molecules has been subsequently performed using unsupervised learning strategy and Kohonen network. The final step of descriptor space testing was supervised learning of Counter-Propagation Artificial Neural Network (CPANN) using n-octanol/water partition coefficient (logP), dipole moment (DM) and molecular refractivity (MR) as target values.

Journal Article↗

PubMedDate not supplied

Molecular modeling study of leflunomide and its active metabolite analogues.

Leflunomide is known as a compound with various sorts of biological activity, which found a practical application in medicine. Search of current literature revealed an active metabolite of Leflunomide together with its eight analogues synthesized as protein tyrosine kinase inhibitors with potential anticancer activity. Accurate description of the molecular structure of these compounds is valuable. The detailed geometrical parameters description was performed using DFT theory. The conformational analysis and intramolecular proton transfer were considered. Using the most stable conformation the detailed electronic structure description was obtained by analysis of electron density and electrostatic potential distribution in the first step. Next, the topological analysis of the electron density by AIM method and electron localization function (ELF) theories supplemented this study. The AIM and ELF theories were applied to study the topology of the molecules, atomic charges distribution, and details of bonding. The theoretical investigations were performed in the gas phase and by using SCRF/PCM solvent reaction field. In this study the molecular modeling results for Leflunomide and the analogues of its active metabolite are presented.

Aniline Compounds↗

PubMedDate not supplied

Synthesis, immunological activity and theoretical study of new 5-substituted 3-methylisoxazole[5,4-d] 1,2,3-triazin-4-one derivatives.

A new series of 5-substituted 3-methylisoxazole[5,4-d] 1,2,3-triazin-4-one derivatives was prepared and investigated. The immunological activities of the studied compounds were investigated in two murine models of the immune response to sheep erythrocytes (SRBC)--the humoral immune response and delayed type hypersensitivity (DTH). Quantum-chemical calculations were carried out using AM1, a semiempirical method for geometry optimization, estimation of descriptors values and localization of the HOMO and LUMO orbitals.

Animals↗

PubMedDate not supplied

Search for new lead structures in the isoxazole heterocyclic system.

Looking for active immunosuppressant, a series of substituted phenylamides of 5-aminomethinimino-3-methylisoxazole-4-carboxylic acid was obtained, which showed immunosuppressory activities in the in vitro and in vivo tests, comparable with that of cyclosporine A. Rentgenostructural studies of three most representative derivatives were performed and the molecular modelling of compounds, demonstrating most characteristic biological activities, was performed. In the next stage, quantum-chemical investigations were conducted in order to determine structure-activity relationships.

Antibody Formation↗