The relationship between structure and antioxidative activity of piperidine nitroxides.
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 (Fe2+-ascorbic acid) in homogenates of liver, heart and kidney of rats, and antagonized H2O2-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'-dinitrophenylhy-drazone-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-tetramethyl 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.
Li
Wen-Guang
WG
School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730 000, PR China.
Zhang
Xiao-Yu
XY
Wu
Yong-Jie
YJ
Gao
Ming-Tang
MT
Zheng
Rong-Liang
RL
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016877:Oxidants; D010880:Piperidines; D008315:Malondialdehyde; C003959:TEMPO