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

这个应用程序的总体目标是继续过去的努力 香精低分子质量水杨酸酯的制备 金属元素铜、锌、锰和铁，并可能使用它们 作为超氧化物歧化酶(SOD)的模拟物。具体目标是：1)综合 亲水亲油平衡可调的有机配体(HLB)，2) 合成这些配体的金属络合物，3)确定配位 系数和这些络合物的类SOD活性，以及4) 确定抗肿瘤和辐射防护/恢复活动 这些复合体中。在人类癌细胞中，铜锌超氧化物歧化酶有时较低 较正常，但MnSOD总是明显压低。它是 因此，有理由期待超氧化物歧化酶模拟具有可调节的 脂类/水的溶解性将具有有益的与健康相关的性质。 这些可能在医学、工业和扩展空间中有用 旅行。所需化合物的合成程序已经确立。 模拟sod活动的确定将使用 黄嘌呤/黄嘌呤氧化酶-硝基蓝超氧化物发生体系 以四唑盐为指示剂。C57BL/6N雄性或雌性小鼠(8至10只 几周后)将在铯-137辐照器中照射。这项工作将 在阿肯色大学医学科学分校完成。这个 抗癌工作将在国家癌症研究所进行。

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.