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.

我们的目的是设计和合成新型核酸基础 含有吡啶型的含有氰基烷基的衍生物 嘌呤或嘧啶循环的氮原子。 蓝氧化 碱的设计可能比相应的2'-更易溶的膜可溶性 已知细胞毒性活性的脱氧核糖核苷。在生物体中， 这些基本衍生物可以根据5'-核苷酸转换为5'-核苷酸 即使在各自的2'-的情况下，也要挽救途径 脱氧核糖核苷激酶的脱氧核苷是较差的底物。 因此，预期蓝核核心碱会显示出更好的细胞毒性 活动比氰基核苷酸的2'-脱氧核糖核苷，是 可行的用作抗肿瘤剂。另一个重要的是 将化合物用于硼中子捕获疗法的潜力 用于治疗癌症。 一般合成的基本原理 提出了蓝核核酸核酸碱基的方法。