RUTHENIUM CONTAINING METALLOPHARMACEUTICALS

经典的钌配位化学最近产生了 特别潜在的医疗保健红利涉及：1） 作为抗癌剂的钌配合物的合理设计 整体作用机制不同于其他金属， 抗癌药 2)简单的钌配合物， 通过抑制T细胞的有效免疫抑制剂 在nanomolar水平增殖。 3)钌的设计 增强电化学长时程增强的复合物 脑组织的反应。 这个实验室的工作有助于促进对 含钌药物的开发， 全球实验室 我们最近发现， 建议的机制，这往往被认为是竞争， 对于钌抗肿瘤剂的作用，可能在 协同促进Ru选择性结合肿瘤细胞DNA。 这 指出了一种可能的新的混合物，金属蛋白 配合物作为活性抗肿瘤剂。 Procept公司最近披露的一项发现，本地 生物技术公司，提出了一种全新的方法， 可以促进移植器官存活的药物， 对抗一些免疫系统疾病，如牛皮癣。 虽然贡献，我们提供的复合物铺平了道路， 发现最活跃的代理人。 我们的结果与亚硝酰配合物的锝建议， 操纵配位亚硝酰基的释放的手段， 热处理和还原后。 一项合作努力 这表明这是可能的，并产生了活性Ru试剂， 促进海马脑片的LTP。 因此， 研究了一系列金属亚硝酰配合物， 强π-受体配体，特别是那些可以作为反式 不稳定剂，将进行，以确定如何NO释放 影响。 控制NO损失的能力应该产生一个新的类 能够穿过膜屏障并释放NO的试剂 在大脑和其他重要位置。

Classical ruthenium coordination chemistry has recently yielded extraordinary potential health care dividends involving: 1) The rational design of ruthenium complexes as anticancer agents with overall mechanisms of action distinct from other metallo- anticancer drugs. 2) simple Ru complexes that are superbly efficient immunosuppressive agents by inhibiting T-cell proliferation at nanormolar levels. 3) The design of a ruthenium complex that enhances the electrochemical long-term-potentiation response in brain tissue. Work in this laboratory has helped to stimulate research into the development of Ru-containing pharmaceuticals in several laboratories worldwide. We have recently shown that two suggested mechanisms, which were often thought to be competing for the action of ruthenium antitumor agents, probably work in concert to promote selective Ru binding to tumor cell DNA. This points the way to a possible new class of hybrid, metalloprotein complexes as active antitumor agents. A recently disclosed discovery by Procept, Inc., a local biotechnology company, suggests an entirely new approach to drugs that could facilitate the survival of transplanted organs and combat some immune-system based diseases such as psoriasis. While contributory, complexes we provided paved the away to the discovery of the most active agents. Our results with nitrosyl complexes of technetium suggested a means of manipulating the release of coordinating nitrosyls both thermally and following reduction. A collaborative effort has shown that this is possible and has yielded an active Ru agent that promotes LTP in hippocampal slices. Consequently, an investigation of a series of metallonitrosyl complexes involving strongpi-acceptor ligands, particularly those which can act as trans labilizers, will be undertaken to determine how NO release is affected. The ability to control NO loss should yield a new class of agents capable of crossing membrane barriers and releasing NO within the brain and at other strategic locations.