Factor analysis (FA) was performed on quinolone derivatives with antibacterial activity to model relationships between molecular descriptors and microbiological activities determined on five bacterial cell lines (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae). Molecular modeling studies were performed with the use of HyperChem software and MM+ molecular mechanics with the semi-empirical AM1 method. Factor analysis led to the extraction of two main factors, with the share of factor 1 amounting to about 76% and factor 2 to about 24% for all the parameters used in the statistical analysis. Moreover, FA results indicated that energy of orbitals lowest unoccupied molecular orbital, energy of ionization, electron affinity, electronegativity, maximum electron density, refraction and polarizability appeared to be descriptors important for the antibacterial activity of quinolones.
The primary aim of this work was to determine the interactions of an oxindole alkaloid (mitraphylline) isolated from Uncaria tomentosa with -amyloid 1-40 (A 1-40 protein) applying the capillary electrophoresis (CE) method. Specifically the Hummel-Dreyer method and Scatchard analysis were performed to study the binding of oxindole alkaloids with A 1-40 protein. Prior to these studies extraction of the alkaloid of interest was carried out. Identification of the isolated alkaloid was performed by the use of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) combined with electrospray ionization mass spectrometry (ESI-MS). The proposed approach was proved to be an efficient and accurate method for specific compound isolation and identification purposes. Moreover, analytical information from the CE approach can be considered as the valuable tool for binding constant determination. The binding constant of mitraphylline with A 1-40 protein determined by the Hummel-Dreyer method and Scatchard analysis equals K = 9.95 ¥ 10 5 m
Ð1. The results obtained showed the significant binding of the tested compound with A 1-40 protein.These results are discussed and interpreted in the view of developing a strategy for identification of novel compounds of great importance in Alzheimer disease therapy.
Differences in drug-melanin interactions were determined for 13 phenothiazine neuroleptics and 2 dibenzazepine thymoleptics by means of high-performance liquid chromatography. The chromatographic column was packed with a stationary phase obtained by chemical immobilization of synthetic L-dopa melanin on silica particles. For six phenothiazines the melanin-binding parameters were also determined by an ultrafiltration method. Correlation between measures of drug-melanin interaction determined chromatographically and by the standard slow-equilibrium method was significant, however moderate. The chromatographic method of assessing interactions between drugs and melanin permitted reliable and quantitatively comparable data for representative series of solutes to be readily obtained. Such data were subjected to the analysis of quantitative structure-retention relationships (QSRR). It was found that retention of the agents on the immobilized melanin column could be described by two-parameter regression equations comprising the energy of the lowest unoccupied molecular orbital and either the water-accessible surface area of a drug molecule or its hydrophobicity parameter, determined chromatographically on an immobilized artificial membrane column. The QSRR equation derived allows for the estimation of melanin binding based on the structure of a compound candidate, and thus rationalizes predictions of potential toxicity of drugs or drug candidates.
Imidazol(in)e compounds show the diversity of pharmacological effects including mydriasis, hypotension, sedation, bradycardia and hypothermia. At first it was postulated that these effects are mediated via α2-adrenoceptors exclusively. Clonidine is well known as a model agent to produce pupillary dilation in rats. However, it became obvious later that clonidine-like imidazol(in)e adrenoceptor agonists which produced mydriasis in rats, exhibit also a high affinity for imidazoline I1-receptors. That short report attempts to review the present status of studies to confirm that the mydriasis model in rats can be a selective system to evaluate the α2-adrenergic activity of potential pharmacologically active compounds of imidazol(in)e structure.
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