A glutathione derivative with chelating and in vitro neuroprotective activities: synthesis, physicochemical properties, and biological evaluation.

Metal-ion dysregulation and oxidative stress have been linked to the progressive neurological decline associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Herein we report the synthesis and chelating, antioxidant, and in vitro neuroprotective activities of a novel derivative of glutathione, GS(HQ)H, endowed with an 8-hydroxyquinoline group as a metal-chelating moiety. In vitro results showed that GS(HQ)H may be stable enough to be absorbed unmodified and arrive intact to the blood-brain barrier, that it may be able to remove Cu(II) and Zn(II) from the Aβ peptide without causing any copper or zinc depletion in vivo, and that it protects SHSY-5Y human neuroblastoma cells against H2 O2 - and 6-OHDA-induced damage.

Peroxisome proliferator-activated receptor-γ mediates the anti-inflammatory effect of 3-hydroxy-4-pyridinecarboxylic acid derivatives: synthesis and biological evaluation.

Seven 3-hydroxy-4-pyridinecarboxylic acid derivatives (HPs), aza-analogues of salicylic acid and structurally close to other potent inflammatory pyridine compounds such as aminopyridinylmethanols and aminopyridinamines, were synthesized, and their anti-inflammatory activity was evaluated. The synthesis was performed by adopting a general procedure involving an intramolecular Diels-Alder cycloaddition of oxazoles with acrylic acid to form various substituted pyridinic acids. The newly synthesized HPs did not exhibit cytotoxic activity on human monocytes-derived macrophages at concentrations up to 10(2) μM.

Different approaches to the study of chelating agents for iron and aluminium overload pathologies.

Our objective is to illustrate the activity of the groups operating in Italy involved in identification and study of new chelating agents, mainly intended for treatment of human pathology correlated with metal overload. The objective of "chelation therapy" is removal of toxic metal ions from the human body or attenuation of their toxicity by transforming them into less toxic compounds or by dislocating them from the site at which they exert a toxic action. Because most of this research activity is related to chelating agents for iron and aluminium, diseases related to these two metal ions are briefly treated.

Perturbations produced by electrospray ionization mass spectrometry in the speciation of aluminium(III)/1,6-dimethyl-4-hydroxy-3-pyridinecarboxylate aqueous solutions.

Electrospray ionization mass spectrometry (ESI-MS) is very often employed to study metal/ligand equilibria in aqueous solution. However, the ionization process can introduce perturbations which affect the speciation results in an unpredictable way. It is necessary to identify these perturbations in order to correctly interpret the ESI-MS speciation results.

Vanadate complexes in serum: a speciation modeling study.

The speciations of two drug candidate ligands, 2-hydroxypyridine-N-oxide (Hhpno) and 2-mercaptopyridine-N-oxide (Hmpno), with vanadate (V(V)) were determined at 25.0 degrees C and 0.20 mol dm(-3) KCl by pH-metric and (51)V-NMR methods.

Use of electrochemical transient techniques to obtain thermodynamic and kinetic data on aqueous Fe(III)-1,6-dimethyl-4-hydroxy-3-pyridinecarboxylate and Fe(III)-4-hydroxy-2-methyl-3-pyridinecarboxylate complexes.

Voltammetric experiments were used to demonstrate the possibility to rapidly obtain stability constants, E degrees values and kinetic parameters of Fe(III) complexes with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) at pH 2.3 and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid (DQ2) at pH 3. Fe(III) diffusion coefficient (D(Fe)= 5.

1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid as new possible chelating agents for iron and aluminium.

1,6-Dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid (DQ2) were evaluated for possible application to iron (Fe) and aluminium (Al) chelation therapy. Metal/ligand solution chemistry, electrochemistry, cytotoxicity, octanol/water partitioning (D(o/w)), and chelation efficiency, were studied. The Fe(iii)/DQ716, Fe(iii)/DQ2, Al(iii)/DQ716, and Al(iii)/DQ2 solution chemistry was investigated in aqueous 0.

Evaluation of 2-methyl-3-hydroxy-4-pyridinecarboxylic acid as a possible chelating agent for iron and aluminium.

In view of a possible application to Fe and Al chelation therapy, 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (DT2) was synthesised, and its complex formation, electrochemical and cytotoxic properties were studied. The complexing properties of DT2 towards Fe(III) and Al(III) were investigated in aqueous 0.6 m (Na)Cl at 25 degrees C by means of potentiometric titrations, UV-vis spectrophotometry, and 1H NMR spectroscopy.