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A series of nineteen novel ring-substituted N -arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against Staphylococcus aureus as the reference strain, two clinical isolates of methicillin-resistant S. aureus (MRSA), and Mycobacterium tuberculosis . (2 E )- N -[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 µM) against MRSA isolates than the commonly used ampicillin (MIC 45.8 µM). The screening of the cell viability was performed using THP1-Blue™ NF-κB cells and, except for (2 E )- N -(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC 50 6.5 µM), none of the discussed compounds showed any significant cytotoxic effect up to 20 μM. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pK a calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

Objectives: To compare two different analytical methods for determination of small dense LDL and to determine a share of corresponding and non-corresponding (inconsistent) results METHODS: In the group of 104 hyperlipidemic patients and 20 healthy individuals of the control group we analysed the total cholesterol and triglycerides by enzymatic CHOD PAP method (Roche Diagnostics, Germany) in EDTA-K2 plasma. Small dense LDL (sdLDL) were quantified by the electrophoretic method for lipoprotein analysis on polyacrylamide gel (PAG) (Lipoprint LDL System, Quantimetrix, CA, USA) and simultaneously, the small dense LDL concentrations in the indentical samples were analysed by an enzymatic method LDL-EX ´Seiken´(Randox, England)., Results: In 31 patients we found the discrepancy in the sdLDL levels using the two different procedures. Out of them, 24 patients tested by enzymatic method ´SEIKEN´ had higher sdLDL values (more than 0.9 mmol/l) compared to the Lipoprint LDL results, which identified normal sdLDL values in the same samples (in 23% of tested patients). In 7 patients out of the 31 tested patients with discrepant sdLDL values, the Lipoprint LDL identified increased values of plasma sdLDL (more than 0.155 mmol/l), while the enzymatic LDL-EX Seiken did not find an increased concentration of sdLDL (in 7% of tested patients). In the control group a discrepancy in the sdLDL results between the two tested analytical methods was not found., Conclusion: The concentration of sdLDL in plasma lipoprotein spectrum obtained by two different laboratory procedures was analysed, compared, evaluated and 70% identical corresponding results have been confirmed.

Glibenclamide, a drug used for the treatment of type 2 diabetes, belongs to Class II of Biopharmaceutical Classification System. It is a highly permeable, but poorly water-soluble drug. Nanoparticles of glibenclamide were prepared by an emulsion solvent evaporation method using dichloromethane as a solvent of glibenclamide and 3% (w/w) aqueous solution of carboxymethyl dextran sodium salt as a stabilizer, which was found as optimal. A solubility test comparing the water solubility of glibenclamide bulk and nanoparticles confirmed the improved (2-fold higher) solubility of glibenclamide nanoparticles (0.045 μ g/ml) compared with bulk (0.024 μ g/ml).

Nanoparticles can be considered as a useful tool for improving properties of poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the Biopharmaceutical Classification System) was chosen as a model compound. Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation methods were used for preparation of 18 samples containing hydrochlorothiazide nanoparticles. Water solutions of surfactants sodium dodecyl sulfate, Tween 80 and carboxymethyl dextran were used in mass concentrations of 1%, 3% and 5%. Acetone and dichloromethane were used as solvents of the model compound. The particle size of the prepared samples was measured by dynamic light scattering. The selected sample of hydrochlorothiazide nanoparticles stabilized with carboxymethyl dextran sodium salt with particle size 2.6 nm was characterized additionally by Fourier transform mid-infrared spectroscopy and scanning electron microscopy. It was found that the solubility of this sample was 6.5-fold higher than that of bulk hydrochlorothiazide.

One approach for the enhancement of oral drug bioavailability is the technique of nanoparticle preparation. Risedronate sodium (Biopharmaceutical Classification System Class III) was chosen as a model compound with high water solubility and low intestinal permeability. Eighteen samples of risedronate sodium were prepared by the solvent evaporation technique with sodium dodecyl sulfate, polysorbate, macrogol, sodium carboxymethyl cellulose and sodium carboxymethyl dextran as nanoparticle stabilizers applied in three concentrations. The prepared samples were characterized by dynamic light scattering and scanning electron microscopy. Fourier transform mid-infrared spectroscopy was used for verification of the composition of the samples. The particle size of sixteen samples was less than 200 nm. Polysorbate, sodium carboxymethyl dextran and macrogol were determined as the most favourable excipients; the particle size of the samples of risedronate with these excipients ranged from 2.8 to 10.5 nm.

The effect of sodium dodecyl sulfate (SDS), an anionic amphiphilic detergent, on the function of human neutrophils and of the human promyelocytic leukemia cell line HL-60 was investigated. SDS modulated the respiratory burst in human neutrophils and HL-60 cells which were stimulated with phorbol 12-myristate 13-acetate (PMA). In concentrations above 1 X 10(-6) M it also caused release of lysosomal enzymes (beta-D-glucuronidase, myeloperoxidase and lysozyme) from neutrophils. Our results demonstrate that SDS at concentrations 1 X 10(-6) M-1 X 10(-4) M strongly affect properties of human phagocytic cells.

The aim of this study was to study the effect of the homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukemia cells. 1-Decylpiperidine N-oxide (deP-NO), one of the active compounds, significantly stimulated the course of aerobic glycolysis of Ehrlich cells. Derivatives with longer side-chains markedly inhibited endogenous respiration of both tumor cells. dePNO, immediately after addition to the suspension of Ehrlich cells in an ice bath, markedly decreased the level of ATP in Ehrlich ascites cells. The decrease in ATP level might be explained through impairment of cell membrane integrity.

The main objective of the present investigation was to screen a series of 1-alkylpiperidine N-oxides for in vitro cytotoxicity, and to find out whether there is a quantitative structure-activity correlation (QSAR) between cytotoxic effect represented here by inhibition of incorporation of [14C]adenine into nucleic acid or [14C]valine into proteins in Ehrlich ascites carcinoma (EAC) cells and structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). On the basis of primary screening, one of the most active compounds, i.e. 1-decylpiperidine N-oxide, was chosen for further biochemical study. The drug inhibited the incorporation rate of 14C-labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium. The lengthening of the alkyl chain in 1-alkylpiperidine N-oxides positively affected their cytotoxic activity in Ehrlich cells. For these compounds the optimal m value is 12-15.

A new class of nonaromatic amine oxides was synthesized and tested for cytotoxic activity in vitro. The aim of this study was to find if there is any correlation between the cytotoxic activity of the investigated 1-alkylpyrrolidine N-oxides and their structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). Maximum activity was achieved with 1-tetradecylpyrrolidine N-oxide (C14) which was chosen for further biochemical studies. Further lengthening led to decrease in activity. The drug inhibited the incorporation rate of [14C] precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich ascites cells, the extent of inhibition being dependent on both time and concentration of the compound in the incubation medium.

A series of new bisquaternary ammonium dibromides of the type N,N'-bis(decyldimethyl)-alpha, omega-alkanediammonium dibromides and N,N'-bis(4-aryloxybutyldimethyl)-1,6-hexane diammonium dibromides has been prepared and screened for antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans. In the first group of compounds the connecting alkyl chain had 2 to 6, 8, 10 and 12 carbon atoms, in the second one in the 4-aryloxybutyl linkage the aryl was phenyl, p-methylphenyl, p-tert-butylphenyl-p-chlorophenyl-1-naphthyl and 2-naphthyl. The effect on the antimicrobial activity of the length of the hydrocarbon chain linking the two nitrogen atoms and the effect of replacing the long alkyl chain with substituted or unsubstituted 4-aryloxybutyl groups was studied.

N,N-Dimethylalkylamines CmH2m+1N(CH3)2 (m = 4 to 18) undergo in vitro N-oxidation to the corresponding amine oxides by mouse liver microsomes. The relative oxidisability of these compounds is parabolically dependent on structural and physico-chemical characteristics (with a maximum at m 12) and is controlled by at least three factors: lipophilicity, stereochemistry and the nucleophilicity of the compounds under evaluation. The results from the QSAR study support this multifactorial view.