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: 3778059
• 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/3778059
• 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.

该应用程序的总体目标是继续过去的努力 制备必需物质的低分子量水杨酸盐 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）模拟物。 具体目标是：1）综合 具有可调节亲水亲油平衡 (HLB) 的有机配体，2) 合成这些配体的金属配合物，3)确定分配 这些复合物的系数和类 SOD 活性，以及​​ 4) 确定抗肿瘤和辐射防护/恢复活动 这些复合物。 在人类癌细胞中，CuZnSOD 有时较低 低于正常值，但 MnSOD 总是明显降低。 这是 那么，期望 SOD 模仿物具有可调节性是合理的。 脂/水溶解度将具有有益于健康的特性。 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很成熟。 SOD 模拟活性测定将通过 黄嘌呤/黄嘌呤氧化酶超氧化物生成系统与硝基蓝 四唑为指示剂。 C57BL/6N 雄性或雌性小鼠（8 至 10 周龄）将在铯 137 辐照器中进行辐照。 这项工作将 在阿肯色大学医学科学分校完成。 这 抗癌工作将在国家癌症研究所进行。