Anticarcinogenic reactivity of copper-dischiffbases with superoxide dismutase-like activity.
CuPu(Py)2 and CuPu(Im)2, two novel dischiffbase coordinated low Mr active centre analogues of Cu2Zn2 superoxide dismutase, were shown to effectively catalyze the production of hydroxyl radicals in the presence and absence of TPA-activated polymorphonuclear leukocytes. These stable copper chelates exhibited a pronounced anticarcinogenic reactivity in male Sprague Dawley rats implanted with Walker 256 carcinosarcoma cells. When four doses of 5 mumol/kg CuPu(Py)2 and CuPu(Im)2, respectively, were administered intratumorally, reduction in tumor size, delay of metastasis and a significant increase in survival of the hosts were observed, resulting in 75% of total remissions. 60% of the animals recovered totally from the carcinosarcoma, when CuPu(Py)2 was applicated intravenously.
Miesel
R
R
Physiologisch-Chemisches Institut, Universität Tübingen, FRG.
Weser
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U
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000473:pathology; D003300:Copper / Q000097:blood; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012074:Remission Induction; D012545:Schiff Bases / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000097:blood / Q000494:pharmacology
D000970:Antineoplastic Agents; D000975:Antioxidants; D005609:Free Radicals; D009942:Organometallic Compounds; D012545:Schiff Bases; C067771:(1,8-di-(2-imidazolyl)-2,7-diazaoctadiene-1,7)-(N,N',N'',N''')-copper(II); D003300:Copper; C064004:N,N'-bis(2-pyridylmethylene)-1,4-butanediamine (N,N',N'',N''')-Cu(II)diperchlorate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D010100:Oxygen