RUTHENIUM CONTAINING METALLOPHARMACEUTICALS

经典的Ru配位化学最近产生了 非同寻常的潜在医疗红利包括：1) Ru配合物抗癌药物的合理设计 整体作用机理有别于其他金属- 抗癌药物。2)简单Ru络合物 抑制T细胞的高效免疫抑制剂 纳米摩尔水平上的增殖。3)Ru的设计 增强电化学长时程增强的络合物 脑组织的反应。 这个实验室的工作帮助刺激了对 几种含Ru药物的研究进展 世界各地的实验室。我们最近展示了两个 建议的机制，通常被认为是相互竞争的 对于Ru抗肿瘤药物的作用，可能在 Concert促进Ru与肿瘤细胞DNA的选择性结合。这 为一类可能的杂交金属蛋白指明了道路 作为活性抗肿瘤药物的络合物。 Procept，Inc.最近披露的一项发现，当地一家 生物技术公司，提出了一种全新的方法来 可以促进移植器官存活的药物和 对抗一些基于免疫系统的疾病，如牛皮癣。 虽然有贡献，但我们提供的综合体铺平了通往 发现最活跃的代理。 我们对亚硝基氚络合物的研究结果表明 操纵配位亚硝基释放的方法 热的和随后的还原。合作的努力产生了 表明这是可能的，并且已经产生了一种活性Ru试剂 促进海马片中的LTP。因此，一个 一系列含氮金属络合物的研究 强pi受体配体，特别是那些可以作为反式配体的配体 将进行实验室检查，以确定不释放的情况 受影响。控制无损失的能力应该会产生一个新的阶级 能够穿透膜屏障并释放NO的试剂 在大脑内和其他战略位置。

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.