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的核酸碱基 含氰基硼烷基的吡啶型衍生物 嘌呤或嘧啶环的氮原子。 氰基硼化 碱可以被设计成比相应的2 ′- 已知具有细胞毒活性的脱氧核糖核苷。在生物体中， 这些碱基衍生物可以根据以下转化为5 ′-核苷酸 即使在各自的2 '- 脱氧核糖核苷是核苷激酶的不良底物。 因此，氰基硼化碱有望显示出更好的细胞毒性， 活性高于氰基硼化2 '-脱氧核糖核苷， 可用作杀虫剂。另一个重要的是， 用于硼中子俘获治疗的化合物的潜力 用于治疗癌症。 一般合成的基本原理 氰基硼化核酸碱基的方法。