On the pharmacology of oxidative burst of human neutrophils.

The effect of three therapeutically used drugs and five polyphenolic compounds on the mechanism of oxidative burst was compared in whole blood and isolated neutrophils at cellular and molecular level. In 10 microM concentration, the compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin (N-f-5HT) > curcumin (CUR) > quercetin (QUER) > arbutin (ARB) > resveratrol (RES) > dithiaden (DIT) > carvedilol (CARV) > brompheniramine (BPA). The ratio between the percentage inhibition of extracellular versus intracellular chemiluminescence (CL) followed the rank order QUER > N-f-5HT > RES > CUR > DIT and is indicative of the positive effect of the compounds tested against oxidative burst of neutrophils, demonstrating suppression of reactive oxygen species extracellularly with minimal alteration of intracellular reactive oxygen species (ROS). Activation of protein kinase C was significantly decreased by DIT, CUR, QUER and N-f-5HT. CARV, DIT, QUER and ARB reduced activated neutrophil myeloperoxidase release more significantly compared with the effect on superoxide anion generation. All compounds tested increased the activity of caspase-3 in cell-free system. It is suggested that other regulatory mechanisms than protein kinase C might participate in the inhibition of neutrophil activation with the compounds tested. Different mechanisms are concerned in controlling the assembly of NADPH oxidase and the regulatory role of calcium ions is suggested. Compounds decreasing the amount of extracellular ROS generation, yet affecting but minimally intracellular ROS generation, are promising for further investigation in vivo.

Antimicrobial effect of 4-hydroxybenzoic acid ester with glycerol.

WHAT IS KNOWN AND OBJECTIVES: Parabens have been commonly used as preservatives in pharmaceutical and cosmetics industries for almost 50 years. These compounds are thermostable, pH-stable and inexpensive and have a wide antimicrobial effect. The antimicrobial activity of parabens in emulsion system is limited by their poor solubility in water phase, which is increasing with the length of their alkyl chain. The aim of this work was preparation of 1-O-(4-hydroxybenzoyl)-glycerol, more hydrophilic and naturally occurring analogue of parabens, and comparison of its antimicrobial activity with commercially used parabens (4-hydroxybenzoic acid, methylparaben, ethylparaben, propylparaben). METHODS: 1-O-(4-Hydroxybenzoyl)-glycerol was obtained by the transesterification reaction of methyl paraben with glycerol. Purity was confirmed by determination of melting point and by GC/MSD. Antimicrobial activity of 1-O-(4-hydroxybenzoyl)-glycerol and commercially used parabens was determined by spectrophotometrical monitoring of microbial growth in media containing the testing substances, using spectrophotometers PowerWave XS and Cary 50 Conc. RESULTS AND DISCUSSION: 1-O-(4-Hydroxybenzoyl)-glycerol was prepared with purity >99%. This compound showed antimicrobial activity against all tested microorganisms (Staphylococcus aureus, Escherichia coli, Saccharomyces cerevisiae and Fusarium culmorum). In comparison with other tested substances, 1-O-(4-hydroxybenzoyl)-glycerol showed less inhibitory activity at the highest concentration of 20 mmol/L, with the maximum inhibitory activity ca. 70%. On the other hand, antimicrobial activity of 1-O-(4-hydroxybenzoyl)-glycerol at the lower concentrations (2·5 mmol/L, 1·25 mmol/L) was the same or, in some cases, even higher (S. aureus) in comparison with commercially used parabens. WHAT IS NEW AND CONCLUSION: A novel hydrophilic analogue of parabens was synthetized and tested for its antimicrobial activity against selected microorganisms in model system. This study confirms antimicrobial potential of 1-O-(4-hydroxybenzoyl)-glycerol, which is comparable with other commercially used parabens. Unlike commercial parabens, it is possible to expect more significant antimicrobial activity of 1-O-(4-hydroxybenzoyl)-glycerol in real emulsion systems due to the increased solubility of this substance in water phase and also the lower skin irritation.

Electrochemical and thermal studies of some quaternary benzo(c) phenanthridine alkaloids.

The conditions of the electrochemical reduction and oxidation as well as those of thermal demethylation of quaternary benzo(c)-phenanthridine alkaloids namely chelerythrine (1), sanguinarine (2), and fagaronine (3) were studied. Differences in their electrochemical and thermal behavior are correlated with the results obtained from biotransformation studies with liver microsomal fraction.