ANTINEOPLASTIC AND RADIOPROTECTANT CU, ZN, MN, AND FE SALICYLATES

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The overall objective of this application is to continue past efforts to prepare the low molecular mass salicylates of the essential metalloelements copper, zinc, manganese, and iron and possibly use them as superoxide dismutase (SOD) mimics. Specific aims are: 1) synthesize organic ligands with adjustable hydrophile-lipophile balance (HLB), 2) synthesize metal complexes of these ligands, 3) determine the partition coefficient and the SOD-like activity of these complexes, and 4) determine the antineoplastic and radiation protection/recovery activities of these complexes. In human cancer cells CuZnSOD is sometimes lower than normal, but the MnSOD is always markedly depressed. It is reasonable, then, to expect that SOD mimics that had adjustable lipid/water solubilities would have beneficial health-related properties. these would possibly be useful in medicine, industry, and extended space travel. Synthetic procedures for desired compounds are well established. SOD-mimetic activity determinations will be done with the xanthine/xanthine oxidase superoxide generating system with nitro blue tetrazolium as the indicator. C57BL/6N male or female mice (8 to 10 weeks old) will be irradiated in a cesium-137 irradiator. This work will be done at the University of Arkansas for Medical Sciences. The anticancer work will be done at the National Cancer Institute.