ANTICAN THIOSEMICARBAZONE COMPXS OF RUTHENIUM&COPPER/SYNTHESIS BIOCHEM&CELLULAR

钌抗硫缩氨基脲络合物

• 批准号: 8168100
• 负责人: FLOYD A BECKFORD
• 金额: $ 13.89万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168100
• 关键词: Antineoplastic Agents; Antiviral Agents; Binding; Biological; Carboplatin; Cell Proliferation; Chemicals; Chemotherapy-Oncologic Procedure; Cisplatin; Clinical Medicine; Complex; Computer Retrieval of Information on Scientific Projects Database; Copper; Coupling; DNA; Data; Development; Ethylenediamines; Funding; Goals; Grant; In Vitro; Institution; Ions; Kinetics; Knowledge; Ligands; Measurement; Medical; Methods; Nucleic Acids; Pharmaceutical Preparations; Platinum; Play; Probability; Property; Reporting; Research; Research Personnel; Resources; Role; Ruthenium; Ruthenium Compounds; Source; Spectrum Analysis; Thermodynamics; Thiosemicarbazones; Transition Elements; United States National Institutes of Health; absorption; base; biological systems; cancer cell; cytotoxic; cytotoxicity; design; improved; metal complex; neoplastic; oncology; prevent; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ultimate aim of this research is to synthesize and characterize new ruthenium and copper complexes with the goal of optimizing their ability to interact with DNA and to establish their ability to disrupt cell proliferation. The key roles that transition metal ions play in biological systems are well established and transition metal complexes are finding increasing usage in clinical medicine including oncology. The platinum-based anticancer drugs cisplatin and carboplatin are the most well known. However, it is important to synthesize new classes of anticancer agents and the design of new potential drugs is increasingly focused on ruthenium complexes. A new class of organometallic ruthenium complexes, [(arene)Ru(XY)Cl]+ (XY = ethylenediamine) have been reported to show significant cytotoxic activity. Copper too has long been used in medical applications and the antitumor properties of some copper complexes have been known since the 1960s. The mechanism of cytotoxicity for ruthenium compounds has not been established. Nucleic acids, particularly DNA, are considered a high probability target. This research is designed to investigate the chemical and biological properties of organometallic and inorganic ruthenium and copper complexes. We aim to establish that we can prepare complexes of the type [Ru(arene)(XY)Cl]+ that can bind to DNA in a predominantly intercalating fashion. In these complexes XY is a class of ligand that includes biologically strategic thiosemicarbazones (TSCs). Thiosemicarbazones have a versatile range of biological effects such as antiviral, anti-neoplastic and anticancer properties, and we expect to see improved biological activity by coupling with the organometallic ruthenium moiety or attachment to a copper center. We will carry out a number of experiments in order to probe the mode as well as strength of binding to the nucleic acid. We expect to also show that the complexes are cytotoxic to cancer cells and are able to prevent proliferation in vitro. The methods to be used include absorption spectroscopy, thermal denaturation studies, electrochemical and viscometric measurements. Mechanistic studies to determine kinetic and thermodynamic data will be done. Successful completion of these goals will add to the body of knowledge concerning inorganic anticancer agents and will deepen our understanding of the mechanisms occurring at the cellular level. This is crucial for further development of these and other cancer chemotherapies.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 这项研究的最终目的是综合和表征新的钌和铜复合物，以优化其与DNA相互作用的能力并确定破坏细胞增殖的能力。过渡金属离子在生物系统中发挥作用的关键作用是良好的，并且过渡金属复合物发现包括肿瘤学在内的临床医学中的使用量增加。铂类抗癌药顺铂和卡铂是最著名的。但是，重要的是合成新的抗癌剂，而新的潜在药物的设计越来越集中于芳族复合物。据报道，一类新的有机金属弦谐谱配合物，[（arene）ru（xy）cl]+（xy =乙二胺）显示出显着的细胞毒性活性。铜也长期以来一直在医疗应用中使用，自1960年代以来，已经知道某些铜复合物的抗肿瘤特性。尚未建立细胞毒性的机制。核酸，尤其是DNA被认为是高概率靶标。这项研究旨在研究有机金属和无机弦齿和铜配合物的化学和生物学特性。我们的目的是确定我们可以准备可以以主要插入方式与DNA结合的[ru（arene）（xy）cl]+类型的复合物。在这些复合物中，XY是一类配体，其中包括生物学策略性硫代硫代氨基酮（TSC）。硫代乳腺癌具有多种生物学作用，例如抗病毒，抗塑料和抗癌特性，我们希望通过与有机金属扁桃部分或附着在铜中心相连，从而改善了生物学活性。我们将进行许多实验，以探测模式以及与核酸结合的强度。我们预计还可以表明，复合物对癌细胞具有细胞毒性，并能够在体外预防增殖。要使用的方法包括吸收光谱，热变性研究，电化学和粘度测量。将进行确定动力学数据和热力学数据的机械研究。这些目标的成功完成将增加有关无机抗癌剂的知识体系，并将加深我们对细胞水平上发生的机制的理解。这对于进一步发展这些癌症化学疗法至关重要。