Patrizia Mazzone

Schiff bases of N-hydroxy-N′-aminoguanidines as antiviral, antibacterial and anticancer agents

Abstract A series of Schiff bases of N -hydroxy- N ′-aminoguanidine tosylate (SB-HAG) were prepared and tested for their in vitro antitumoral, antiviral and antibacterial activities. Several compounds displayed a weak anticancer activity and an interesting activity against viruses.

Inhibition of rat liver mitochondrial monoamine oxidase by hydrazine-thiazole derivatives: structure-activity relationships.

The purpose of this research is to study the relationship between chemical structure and inhibitory activity of some hydrazine-thiazole derivatives on rat liver mitochondria monoamine oxidase (MAO). Forty-five compounds belonging to three series of hydrazine-thiazole derivatives, with either alkylic or arylic substituents in the thiazole ring, were tested. The highest inhibitory activity was observed with piperonyl derivatives 25 and 40, which contain a 4-methyl group in the thiazole nucleus. The structure-activity relationship of MAO inhibitors was established in relation to hydrophobic, electronic and steric hindrance parameters. A mechanism of enzyme inhibition was proposed based on the calculation of HOMO energies.

Interaction of monoamine oxidase inhibitors with dipalmitoyl phosphatidylcholine liposomes. A comparison between structure and calorimetric data

Abstract The effect exerted by some 1-alkoxybenzylidene-(4-toluyl-thiazol-2-yl)-hydrazines possessing monoamine oxidase inhibitory (MAOI) activity, on the thermotropic behaviour of model membranes constituted by dipalmitoylphosphatidylcholine (DPPC) vesicles, was studied by Differential Scanning Calorimetry (DSC). Attention was directed to evaluate eventual modifications in drug-lipid interaction induced by drug structural variations. The examined drugs, as hydrobromide compounds and their free bases, were found to modify the gel-to-liquid crystal phase transition of DPPC liposomes, by causing a shift of the transition temperature (Tm) towards lower values and a negligible variation in the enthalpy changes ( ΔH ). These modifications were a function of the drug concentration. These effects were differently modulated by the substituents present in the drug molecule backbone. Differences should be caused by the different polarity and pH influence of the salt or free base form. The calorimetric results could be related to MAO inhibitory activity measured by fluorescence techniques. The hypotheses on a relation between drugs structure, inhibitory activity and membrane interaction are suggested.

THIAZOLE DERIVATIVES AS INHIBITORS OF PURIFIED BOVINE LIVER MITOCHONDRIAL MONOAMINE OXIDASE-B : STRUCTURE-ACTIVITY RELATIONSHIPS AND THEORETICAL STUDY

Structure-activity relationships were performed on a new series of thiazole derivatives which selectively inactivate monoamine oxidase-B (MAO-B), purified from mitochondrial beef liver. All of the synthesized and tested compounds showed non-competitive inhibition, suggesting the formation of a stable adduct between the tertiary amine function, linked to the thiazolyl derivatives and the active site of the enzyme. The mechanism of MAO-B inhibition is discussed in terms of the Ionization Potential of the amine nitrogen atom and the conformational flexibility of the inhibitors.