Open AccessThe relationship between structure and antioxidative activity of piperidine nitroxides
Author(s) -
Li WenGuang,
Zhang XiaoYu,
Wu YongJie,
Gao MingTang,
Zheng RongLiang
Publication year - 2006
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1211/jpp.58.7.0009
Subject(s) - piperidine , chemistry , phenylhydrazine , haemolysis , isothiocyanate , medicinal chemistry , stereochemistry , superoxide , nitroxide mediated radical polymerization , biochemistry , organic chemistry , enzyme , radical polymerization , copolymer , immunology , polymer , biology
We have investigated the relationship between structure and antioxidative activity of piperidine nitroxides which were substituted by different groups at the 4‐position. All of the tested piperidine nitroxides inhibited malondialdehyde (MDA) generation caused either spontaneously or by a hydroxyl free radical generation system (Fe 2+ ‐ascorbic acid) in homogenates of liver, heart and kidney of rats, and antagonized H 2 O 2 ‐induced haemolysis from rat erythrocytes in a concentration‐dependent manner. The same rank was followed: Bis‐(4‐amino‐2,2,6,6‐tetramethyl piperidinooxyl) (4‐BIS‐Tempo) and 4‐azido‐2,2,6,6‐tetramethyl piperidinooxyl (4‐N 3 ‐Tempo) >4‐isothiocyanate‐2,2,6,6‐tetramethyl piperidinooxyl (4‐ISO‐Tempo), 4‐2′,4′‐dinitrophenyl‐hydrazone‐2,2,6,6‐tetramethyl piperidinooxyl (4‐D‐Tempo), 4‐sulfonate‐2,2,6,6‐tetramethyl piperidinooxyl (4‐S‐Tempo) and 4‐amino‐2,2,6,6‐tetramethyl piperidinooxyl (4‐NH 2 ‐Tempo) > 4‐acetate ester‐2,2,6,6‐tetramethyl piperidinooxyl (4‐A‐Tempo) and 4‐benzoate‐2,2,6,6‐tetra‐methyl piperidinooxyl (4‐B‐Tempo). With the exception of 4‐A‐Tempo and 4‐D‐Tempo, the tested piperidine nitroxides inhibited superoxide anion (O 2 .‐ ) release from neutrophils stimulated by zymosan. The concentration required for inhibiting O 2 .‐ release was higher than that of inhibiting MDA formation and haemolysis. However, 4‐amino‐2,2,6,6‐tetramethyl piperidine (4‐NH2‐TempH) and other 4‐position substitutes, such as NaN3 and isothiocyanate, had no effects on MDA formation, haemolysis or O 2 .‐ release. The results indicated that nitroxides have a wide range of scavenging reactive oxygen species (ROS) actions. The nitroxide moiety was the essential group while the 4‐position substitutes could influence the activity of nitroxides on scavenging ROS.