Novel iron complexes behave like superoxide dismutase in vivo.
Novel iron and copper complexes having tris[N-(5-methyl-2-pyridylmethyl)-2-aminoethyl]amine (5MeT-PAA), tris[N-(3-methyl-2-pyridylmethyl)-2-aminoethyl]amine (3MeTPAA), tris[N-(5-methoxycarbonyl-2-pyridylmethyl)-2-aminoethyl]amine (TNAA), tris[(2-thienylmethyl)-2-aminoethyl]amine (TTAA), tris[(2-furylmethyl)-2-aminoethyl]amine (TFAA) or tris[(2-imidazoyl)-2-aminoethyl]amine (TIAA) as ligand, were synthesized to examine the superoxide dismutase (SOD) activity. The concentrations of Fe-3MeTPAA and Fe-TIAA equivalent to 1 unit of SOD (IC50) were 0.5 microM and 1.0 microM, respectively. Fe-3MeTPAA and Fe-TIAA had higher SOD activity than other Fe and Cu complexes and protected Escherichia coli cells from paraquat toxicity. In case of using tris[N-(6-methyl-2-pyridylmethyl)-2-aminoethyl]amine (6MeTPAA) as ligand, the Fe complex could not be obtained, which may be due to the steric hindrance of 6-methyl substituent. Generally, Cu complexes had low SOD activity, compared with Fe complexes, and could not suppress paraquat toxicity.
Nagano
T
T
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Hirano
T
T
Hirobe
M
M
D003300:Copper / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000378:metabolism* / Q000494:pharmacology; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D009942:Organometallic Compounds; D013481:Superoxides; D003300:Copper; D007501:Iron; D013482:Superoxide Dismutase; D010269:Paraquat