具有抗肿瘤活性的金属钌配合物与人血清白蛋白相互作用研究

发布时间：2018-04-01 13:33

本文选题：钌配合物　切入点：姜黄素　出处：《广西师范学院》2017年硕士论文

【摘要】：顺铂和卡铂是目前临床使用最为广泛的抗肿瘤药物之一,但此类药物毒副作用大、生物相容性差、并且只能注射给药,而钌类配合物具有易吸收、易代谢、易功能化及抗癌谱广的优势。类姜黄素衍生物和缩氨基硫脲类化合物是两类被验证可以用来调节配合物生物活性和药理活性的配体。并且这两类化合物均具有良好的抗癌活性。本论文研究了以类姜黄素衍生物和缩氨基硫脲类化合物为配体的金属钌配合物与人血清白蛋白的相互作用,对设计和开发新型金属钌类抗癌药物具有重要的指导意义。本论文运用光谱法、液相色谱-质谱联用法,系统研究了两种类姜黄素衍生物配体的芳基钌配合物、一种芳基钌前体化合物和两种单核氨基硫脲芳基钌配合物、两种双核氨基硫脲芳基钌配合物与人血清白蛋白的相互作用。稳态荧光光谱结果表明,七种复合物通过静态猝灭机制使人血清白蛋白(HSA)的内源荧光猝灭。范德华力和氢键为形成稳定基态复合物的重要因素。芳基钌复合物的加入使HSA的结构和微环境发生了明显改变。氨基硫脲苯环上取代基的差异、姜黄素噻吩环上取代基的差异、芳基钌的个数及其导致的空间位阻可能是引起复合物与人血清白蛋白作用存在差异的原因。对金属钌配合物结构的研究有助于理解复合物的生物效应,对设计、研发及筛选以蛋白质为靶标分子的高效金属钌配合物的具有重要指导意义。
[Abstract]:Cisplatin and carboplatin are one of the most widely used anticancer drugs in clinic at present. However, these drugs have great toxicity and poor biocompatibility, and can only be injected into the drug, while ruthenium complexes are easy to absorb and metabolize. Curcumin derivatives and thiosemicarbazones are two kinds of ligands that have been proved to regulate the biological and pharmacological activities of the complexes. The interaction of ruthenium complexes with curcumin derivatives and thiosemicarbazones as ligands with human serum albumin (HSA) was studied. In this paper, the aryl ruthenium complexes of two kinds of curcumin derivatives ligands were studied by spectroscopic method and liquid chromatography-mass spectrometry. The interaction between an aryl ruthenium precursor compound, two mononuclear thiosemicarbazone aryl ruthenium complexes and two binuclear thiosemicarbazone aryl ruthenium complexes with human serum albumin. The seven complexes quench the endogenous fluorescence of human serum albumin (HSA) by static quenching mechanism. Van der Waals force and hydrogen bond are important factors in the formation of stable ground state complex. The addition of aryl ruthenium complex makes the structure and microenvironment of HSA. The difference of substituents on thiosemicarbazone ring, The difference of substituents on curcumin thiophene ring, The number of aryl ruthenium and the steric hindrance caused by aryl ruthenium may be the reasons for the difference between the complexes and human serum albumin. The study of the structure of ruthenium complexes is helpful to understand the biological effects of the complexes and to design them. It is of great significance to develop and screen highly effective ruthenium complexes targeting proteins.
【学位授予单位】：广西师范学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O641.4;TQ460.1

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