Free radical scavenging and metal chelating activity of some therapeutic heterocyclic agents

There is evidence that endogenous oxidative damage to biological important target molecules, such as proteins, lipids and DNA, is an important factor in the development of many chronic diseases (i.e. cancer,cardiovascular and inflammatory pathologies, atherosclerosis). Reactive oxygen species (ROS),which are constantly formed in human body, can become toxic when generated in excess or in the presence of a deficiency in the naturally occurring antioxidant defences. The presence of transition metals (i.e. iron and copper) enhances the ROS toxicity by o-catalysing the conversion of O2 and H2O2 into more oreactive and harmful OH radicals. Some chemicals, developed for specific therapeutic purposes, have shown also useful antioxidant activity, hence limiting the injury caused by free radicals or, indirectly, by catalytic metal ions. This review overviews the approaches we have used to characterise, in model chemical systems, some antioxidants properties of natural and synthetic heterocyclic nitrogen-containing compounds, such as carnosine, captopril, allopurinol, and melatonin. In fact, these compounds are often reported to exert their pharmacological action also by mechanisms referable to those of antioxidants. Their possible antioxidant role as radical scavengers and metal-ion binders have been extensively studied by means of radiation chemistry (pulse radiolysis) and vibrational spectroscopic (Raman and IR) techniques.