Neopterin derivatives modulate toxicity of reactive species on Escherichia coli.

Neopterin and 7,8-dihydroneopterin are released by human monocytes/macrophages upon stimulation with interferon-gamma. In parallel, a panel of highly reactive species is produced by macrophages as part of their cytotoxic armature, which is directed against microbial and viral challenge and against malignant growth. Recently, neopterin and 7,8-dihydroneopterin were shown to modulate the action of reactive species in vitro.

Inhibition of xanthine oxidase by pterins.

The effect of a panel of pterins on xanthine oxidase was investigated by measuring formation of urate from xanthine as well as formazan production from nitroblue tetrazolium. The pterin derivatives, depending on their chemical structure, decreased urate as well as formazan generation: 200 microM neopterin and biopterin suppressed urate formation (90% from baseline) and formazan production (80% from baseline) as well. Their reduced forms, 7,8-dihydroneopterin and 5,6,7,8-tetrahydrobiopterin, showed a lesser but still strongly diminishing influence (40% from baseline).

Neopterin derivatives modulate the nitration of tyrosine by peroxynitrite.

The impact of neopterin and 7,8-dihydroneopterin on peroxynitrite-induced nitration of l-tyrosine was studied. Neopterin derivatives and peroxynitrite are formed during immune response. Tyrosine nitration represents one major effect of nitric oxide-mediated cytotoxicity.