title: The relationship between structure and antioxidative activity of piperidine nitroxides.
abstract: 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.
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730 000, PR China.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Li
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wu
authors.forename: Ming-Tang
authors.initials: MT
authors.lastname: Gao
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Zheng
mesh_terms: 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
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D016877:Oxidants; D010880:Piperidines; D008315:Malondialdehyde; C003959:TEMPO