Pteridine derivatives as modulators of oxidative stress

Pteridine derivatives which have a widespread occurrence in nature have been investigated upon their interactions with free radicals and free radical mediated reactions utilizing a number of different experimental systems. Searching for biological functions, which are still unknown for the majority of pteridine compounds, the effect of pteridines in systems like luminol-induced chemiluminescence, enzyme activity, DNA photodamage, EPR experiments or radical induced injury--just to name a few--have been investigated. The general view during the initial phase of investigations on this special field was, that reduced pterins, i. e., tetra- as well as dihydropterins, generally act as radical scavengers, while aromatic pterins, if not inactive, exert radical promoting activity. Meanwhile the data available provide a more complex view: pteridines of all oxidation states have been shown to act anti- or prooxidatively, depending on the special conditions of the experiment. The reason is that reduced pterins, besides of being scavengers of free radicals, also are strongly reducing agents and therefore, in the presence of transition metal ions promote Fenton chemistry. Aromatic pterins have been described as inhibitors or substrates of enzymes involved--in vitro and in vivo--in free radical generation. Together with the unknown local concentrations of, e.g., neopterin and dihydroneopterin occurring in vivo, these reasons make it impossible to unequivocally predict a physiological net effect of pterins of different oxidation states concerning free radical mediated reactions in real biological systems.