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

抗肿瘤剂和放射防护剂 CU、ZN、MN 和 FE 水杨酸盐

• 批准号: 3756115
• 负责人: WILLIAM M WLLINGHAM
• 金额: --
• 依托单位: UNIVERSITY OF ARKANSAS AT PINE BLUFF
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3756115
• 关键词: antineoplastics; copper; drug design /synthesis /production; drug screening /evaluation; heavy metals; iron; laboratory mouse; manganese; metal complex; radioprotective agents; salicylate; superoxide dismutase; zinc

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.

本申请的总体目标是继续过去的努力， 制备必需的低分子量水杨酸酯， 金属元素铜，锌，锰和铁，并可能使用它们 超氧化物歧化酶（SOD）模拟物。 具体目标是：1）综合 具有可调节的亲水亲油平衡（HLB）的有机配体，2） 合成这些配体的金属配合物，3）确定分配 系数和这些复合物的SOD样活性，和4） 确定放射性和辐射防护/恢复活动 这些复合物。 在人类癌细胞中，CuZnSOD有时低于 但MnSOD总是明显降低。 是 合理的，然后，期望SOD模仿具有可调节的 脂/水溶解度将具有有益的健康相关性质。 这在医学、工业和扩展空间方面可能是有用的 出行 所需化合物的合成方法已得到充分确立。 SOD模拟活性测定将使用 硝基蓝黄嘌呤/黄嘌呤氧化酶超氧化物生成系统 四唑作为指示剂。 C57 BL/6 N雄性或雌性小鼠（8至10只 几周大）将在铯-137辐射器中进行辐射。 这项工作将 在阿肯色州大学医学系完成。 的 抗癌工作将在国家癌症研究所进行。