POTENTIAL ANTI-TUMOR TRANSITION METAL COMPLEXES

潜在的抗肿瘤过渡金属配合物

• 批准号: 3777860
• 负责人: MARIEL M MUIR
• 金额: --
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777860
• 关键词: X ray crystallography; antineoplastics; cell membrane; chemical structure function; cis platinum compound; cytotoxicity; drug design /synthesis /production; drug interactions; gold; human subject; infrared spectrometry; iridium; metal complex; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; nucleobase; nucleotides; palladium; rhodium; stereochemistry; sulfur compounds; ultraviolet spectrometry

New complexes of Pt(II) which represent potential third-generation anti- tumor drugs will be prepared and compared to the widely used drug cisplatin, cis-Pt(NH3)2Cl2 and its second-generation analogs. The principal objectives are to find new complexes which do not show cross- resistance in tumors which are resistant to cisplatin. Carrier ligands to be used in preparing the complexes will include heterocyclic amines such as thiazole and imidazole derivatives which have their own biological activities. Tethered ligands in which quinolinium ions with anti-tumor activity are linked to the carrier ligands through flexible chains will also be studied. Possible intercalators may also be used in preparation of complexes with tethered ligands. Variations in leaving groups will be used to improve the aqueous solubilities of the complexes. Related complexes with other metals such as Rh, Ir, Au, and Ru will be prepared and all will be screened for cytotoxicity. Complexes will be characterized by spectroscopic and X-ray diffraction methods. The interactions of the complexes will be studied with nucleobases, sulfur-containing reagents, DNA, and cell membranes.

代表潜在的第三代抗肿瘤药物的Pt（II）的新络合物 将制备肿瘤药物并与广泛使用的药物进行比较 顺铂、顺式-Pt（NH3）2Cl 2及其第二代类似物。 的 主要目标是找到新的配合物，不显示交叉- 对顺铂耐药的肿瘤中的耐药性。 载体配体 用于制备络合物的化合物将包括杂环胺， 噻唑和咪唑衍生物具有其自身的生物活性， 活动 其中喹啉鎓离子具有抗肿瘤活性的栓系配体 活性通过柔性链与载体配体连接， 也被研究。 可能的嵌入剂也可用于制备 与栓系配体的配合物。 将使用离去基团的变化 以改善配合物的水溶性。 相关络合物 与其它金属如Rh、Ir、Au和Ru一起制备，并且所有金属都将 进行细胞毒性筛查。 复合体的特征是 光谱和X射线衍射方法。 的相互作用 复合物将与核碱基，含硫试剂， DNA和细胞膜。