Substituent Effects of Pterin Derivatives on Singlet Oxygen Scavenging Activity

The relationship of chemical structures of 6-formylpterin (6FP) and its derivatives with scavenging activity of singlet oxygen (O-1(2)) was examined. First, effects of pterin derivatives on O-1(2) released from activated human neutrophils were examined. The neutrophils, stimulated with opsonized zymosan, released O-1(2) that was detected by chemiluminescence using a O-1(2) specific probe, trans-1-(2'-methoxyvinyl)pyrene. 6FP and its derivatives suppressed the O-1(2) release. 6FP and other commercially available pterin derivatives, such as biopterin and neopterin, which have different substitutions at the 6-position, suppressed the O-1(2) release with similar extent. On the other hand, newly synthesized pterin derivatives, which have different substitutions at the 2- and/or 3-position, such as 2-amino-6-formyl-3-methylpteridin-4-one, suppressed the O-1(2) release in a dose-dependent manner and more potently than 6FP. Then, the O-1(2) scavenging activity of pterin derivatives was examined photochemically by direct analysis of near-infrared luminescence at 1270 nm, the most sensitive method for the detection of O-1(2). When rose Bengal, a photosensitizer, in D2O solution, was irradiated by 514 nm laser beam, the emission spectrum of O-1(2) was observed. 6FP suppressed this emission spectrum of O-1(2), and the newly synthesized pterin derivatives with different substituent at the 2- and/or 3-position suppressed the spectrum more potently than 6FP. The order of potency was similar to that obtained from biological assays. These findings indicate that the substitutions at the 2- and/or 3-position play an important role in O-1(2) scavenging activity of pterin derivatives.