Use of reversed-phase liquid chromatography for determining the lipophilicity of alpha-aryl-N-cyclopropylnitrones.

The relationship between a reversed-phase high-performance liquid chromatography (RP-HPLC) retention parameter and various calculated log P-values of our previously synthesized alpha-aryl-N-cyclopropyl-nitrone derivatives was investigated. The RP-HPLC experiments were carried out with acetonitrile-water and methanol-water mixtures as mobile phases and with two kinds of stationary phases of different polarity. The retention parameter, log k(w) was obtained by linear extrapolation of the log k retention to pure water as the mobile phase. The calculated log P-values were C log P, ACD/log P, R log P, A log P, LogKow, X log P and M log P. Statistically, highly significant correlations were found between log k(w) and the calculated log P-values with squared correlation coefficients ranging from 0.771 (with A log P) to 0.956 (with C log P). In addition, the comparative molecular similarity indices analysis (CoMSIA) method was also applied to correlate the log k(w) retention parameter of the compounds with their molecular fields. Statistically significant CoMSIA models were obtained between log k(w) and the hydrophobic and steric molecular fields of our compounds. The CoMSIA models describe how the structure of the nitrone derivatives influences (through hydrophobic and steric interactions with the stationary phase) the chromatographic retention of the compounds.

Glycosaminoglycans inhibit neurodegenerative effects of serum amyloid P component in vitro.

Serum amyloid P component, a member of pentraxin serum protein family, has been suggested to contribute to the progression of neurodegeneration including Alzheimer's disease by binding to beta-amyloid fibrils leading to an increased stability of the deposits against proteolytic degradation and by inducing neuronal apoptosis. Here, we show that glycosaminoglycans inhibit both the serum amyloid P component-beta-amyloid interaction and the neurotoxic effect of serum amyloid P component. These effects correlate with the structure of glycosaminoglycans and show different structure-activity relationship in the case of the two different effects. While the efficacy of the inhibition on the serum amyloid P component-induced cell death increases with the uronic acid content, the inhibitory activity on the serum amyloid P component-beta-amyloid interaction decreases with the increasing uronic acid content of the glycosaminoglycans. The inhibitory effect of glycosaminoglycans on the interaction between the first component of the complement cascade (C1q) and beta-amyloid shows a similar structure-activity relationship as on the serum amyloid P component-beta-amyloid interaction. This suggests that glycosaminoglycans interfere with the binding site on beta-amyloid for serum amyloid P component and C1q. The functional consequence of this binding has been demonstrated by heparin which promotes the proteolysis of beta-amyloid in vitro in the presence of serum amyloid P component. Our results suggest that glycosaminoglycans might have therapeutical potential on the neurodegeneration reducing its progress.

Effect of different metal ions on the oxidative damage and antioxidant capacity of hyaluronic acid.

Degradation and the antioxidative effect of Na-, Zn-, Co-, Cu-, and Mn-hyaluronic acid (HA) associates were studied. Our findings revealed the protective effect of certain counterions against ROS-induced HA degradation. We could also separate the antioxidative effect of certain counterions from that of the HA by examining the effect of the counterions in their free ionic forms. The result showed that metal ions with altering oxidative status (Co(2+), Cu(2+), Mn(2+)) proved to be effective in themselves or their effect added to that of HA when HA was also effective. Moreover, the effects of Co-HA against z.rad;O(2)(-) and of Mn-HA against ONOO(-) as well as the synergic effect of Zn-HA associates where Zn(2+) is of fixed oxidative status were attributed to the structure-stabilizing complex formed between certain counterions and HA. Our examination also concerned the influence of HA associates on the indirect antioxidation related to Fe(2+) chelating. The individual effects of Zn(2+), Co(2+), and Cu(2+) were only detectable, which could be explained by the competitive displacement of ferrous from its binding site.