Copper(II)[2,3-butanedionebis(N4-methylthiosemicarbazone)], a stable superoxide dismutase-like copper complex with high membrane penetrability.
To obtain a superoxide dismutase (SOD)-like drug that could readily cross the cell membrane, we investigated the SOD-like activity, intracellular uptake, and stability of several Cu(II)Bisthiosemicarbazones (Cu(II)BTS). Among these Cu(II)BTS chelates, Cu(II)[2,3-Butanedionebis(N4-methylthiosemicarbazone)] (Cu(II)BMTS) was the most effective SOD-like compound with activity similar to activity reported for various previously reported SOD-like Cu complexes. Biodistribution studies in mice indicated that Cu(II)BMTS rapidly distributed to all tissues and readily crossed cell membranes as well as the blood-brain barrier with high distributions to the brain and the heart. Moreover, Cu(II)BMTS was stable in mouse brain homogenate and mouse blood. These results suggest that Cu(II)BMTS has the potential to be used as a SOD-like drug capable of reaching intracellular superoxide generating sites.
Wada
K
K
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Fujibayashi
Y
Y
Yokoyama
A
A
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics*; D003301:Copper Radioisotopes; D003574:Cytochrome c Group / Q000378:metabolism; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010539:Permeability; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013882:Thiosemicarbazones / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D003301:Copper Radioisotopes; D003574:Cytochrome c Group; D009942:Organometallic Compounds; D013778:Tetrazolium Salts; D013882:Thiosemicarbazones; D014970:Xanthines; C086817:copper(II) (2,3-butanedionebis(N(4)-methylthiosemicarbazone)); C042207:4-anisyltetrazolium blue; D019820:Xanthine; D003300:Copper; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase