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 ((1)O(2)) was examined. First, effects of pterin derivatives on (1)O(2) released from activated human neutrophils were examined. The neutrophils, stimulated with opsonized zymosan, released (1)O(2) that was detected by chemiluminescence using a (1)O(2) specific probe, trans-1-(2'-methoxyvinyl)pyrene. 6FP and its derivatives suppressed the (1)O(2) release. 6FP and other commercially available pterin derivatives, such as biopterin and neopterin, which have different substitutions at the 6-position, suppressed the (1)O(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 (1)O(2) release in a dose-dependent manner and more potently than 6FP. Then, the (1)O(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 (1)O(2). When rose Bengal, a photosensitizer, in D(2)O solution, was irradiated by 514 nm laser beam, the emission spectrum of (1)O(2) was observed. 6FP suppressed this emission spectrum of (1)O(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 (1)O(2) scavenging activity of pterin derivatives.
Mori
Hiroko
H
Department of Anesthesia, Higashiyama Takeda Hospital, Kyoto 605-0932, Japan.
Nishinaka
Yoko
Y
Nonogawa
Mitsuru
M
Sommani
Piyanart
P
Makino
Keisuke
K
Yamashita
Kouhei
K
Arai
Toshiyuki
T
D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011622:Pterins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012395:Rose Bengal; D026082:Singlet Oxygen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015054:Zymosan / Q000494:pharmacology
D016166:Free Radical Scavengers; D011622:Pterins; D026082:Singlet Oxygen; D012395:Rose Bengal; D015054:Zymosan