DRUG/DNA INTERACTION USING SERS

硫唑嘌呤，AZA，6-巯基嘌呤，6 MP的缓释前药，是一种抗肿瘤药物。 用于治疗人类白血病的已确立的临床药剂。沿着 由于其抗肿瘤活性，AZA也被广泛用作 免疫抑制剂在预防各种移植排斥反应中的应用 器官以及抗炎剂治疗类风湿性关节炎 关节炎除了它的生物学意义， AZA与金属的化学反应也很重要，因为分子 提供了许多通用的结合位点，这些位点可能能够 与金属配合。初步研究了一些这些AZA- 金属络合物已经确定它们具有抗肿瘤活性， 在某些情况下大于母体分子。 本研究的目的是了解选择性结合的性质， Aza，6 mp，它们的复合物和类似物，目的是澄清 药物的化疗活性与其协同作用之间的联系 化学.影响结合位点选择的因素 AZA、6 MP、它们的络合物和类似物与银的结合 将使用表面增强拉曼光谱研究表面， 而AZA-金属配合物与DNA之间的相互作用将是 研究使用吸收光谱和表面增强拉曼 谱 该研究将结合位点的影响与 电负性和立体化学的限制，对模式的 AZA及其金属配合物与银表面的相互作用， 用DNA这项研究将扩大现有的知识药物金属 相互作用，了解这一点对于理解 影响体内金属转运的因素。这些互动一直是 显示出在开发缓释或缓释制剂中的重要考虑因素， 长效药物 mdAZA-金属配合物与DNA相互作用模式的阐明 将确定负责药物 两个主要的化学治疗特征，其细胞毒性和抑制 细胞增殖建立药物与 分子结构及其细胞毒性将有助于 设计和合成具有降低的细胞毒性的新药。

Azathioprine, AZA, a slow release prodrug of 6-mercaptopurine, 6MP, is an established clinical agent for the treatment of human lukemias'. Along with its anti-tumor activity AZA is also widely used as an immunosuppressant in the prevention of rejection of various transplanted organs as well as an anti-inflammatory agent in the treatment of rheumatoid arthritis. Apart from it's biological significance, the coordination chemistry of AZA with metals is also significant because the molecule offers a number of versatile binding sites which are potentially capable of coordinating with metals. Preliminary studies on a number of these AZA- metal complex have established them as possessing anti-tumor activity, in some cases greater than that of the parent molecule. This study is aimed at understanding the selective binding properties of Aza, 6mp, their complexes and analogues, with the intent of clarifying the link between the drug's chemotherapeutic activity and its coordination chemistry. The factors affecting the choice of binding sites involved in the binding of AZA, 6MP, their complexes and analogues with a silver surface will be investigated using surface-enhanced Raman spectroscopy, while the interaction between AZA-metal complexes and DNA will be investigated using absorption spectroscopy and surface-enhanced Raman spectroscopy. The proposed study will correlate the effect of binding site electronegativity and stereochemical constraints, on the mode of interaction of AZA and its metal complexes with a ilver surface and also with DNA. This study will expand on the existing knowledge on drug metal interactions, a knowledge of which is important in understanding the factors affecting in vivo metal transport. These interactions have been shown to be important considerations in the development of slow release or long acting drugs. Elucidation of the mode of interaction of md AZA-metal complexes and DNA will identify the molecular parameters which are responsible for the drug's two main chemotherapeutic features, its cytotoxicity and inhibition of cellular proliferation. Establishment of a correlation between the drug's molecular structure and its cytotoxicity would be instrumental in the design and synthesis of new drugs possessing reduced cytotoxicity.