BORONATED NUCLEOSIDE BASES

硼化核苷碱基

• 批准号: 3493427
• 负责人: BERNARD F SPIELVOGEL
• 金额: $ 5万
• 依托单位: BORON BIOLOGICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1993-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3493427
• 关键词: antineoplastics; boron; chemical synthesis; chemistry; chromatography; cyanides; lipid solubility; membrane permeability; neutron radiation; nucleobase analog; radionuclide therapy

Our objective is to design and synthesize novel nucleic acid base derivatives containing cyanoborane group attached to a pyridine-type nitrogen atom of the purine or the pyrimidine cycle. The cyanoboronated bases may be designed to be more membrane soluble than the respective 2'- deoxyribonucleosides of known cytotoxic activities. In living organisms, these base derivatives may be converted to the 5'-nucleotides according to salvage pathways, even in cases when the respective 2'- deoxyribonucleosides are poor substrates for nucleoside kinases. Therefore, the cyanoboronated bases are expected to show better cytotoxic activities than the cyanoboronated 2'-deoxyribonucleosides and are feasible to use as antineoplastic agents. An additional importance is the potential for the compounds to be used in boron neutron capture therapy for the treatment of cancer. A rationale for the general synthetic approach to cyanoboronated nucleic acid bases is presented.

我们的目标是设计和合成新型的核酸碱基 含有连接在吡啶型上的氰基的衍生物 嘌呤或嘧啶环中的氮原子。氰化硼 碱基可以被设计成比各自的2‘-更易膜溶解 已知细胞毒活性的脱氧核糖核苷。在有生命的有机体中， 这些碱基衍生物可以转化为5‘-核苷酸 抢救道路，即使在各自的2‘- 脱氧核糖核苷是核苷酶的不良底物。 因此，氰基硼碱基有望表现出更好的细胞毒性。 比氰化硼2‘-脱氧核糖核苷的活性更高 可作为抗肿瘤药物使用。另外一个重要的是 化合物在硼中子俘获治疗中的应用前景 用于治疗癌症。关于一般合成的基本原理 提出了一种合成氰基硼化核酸碱基的方法。