用于癌症治疗和成像的 N3-取代的胸苷生物缀合物。
N3-substituted thymidine bioconjugates for cancer therapy and imaging.
机构信息
Division of Medicinal Chemistry & Pharmacognosy, The Ohio State University, Columbus, OH 43210, USA.
出版信息
Future Med Chem. 2013 Apr;5(6):677-92. doi: 10.4155/fmc.13.31.
Abstract
The compound class of 3-carboranyl thymidine analogues (3CTAs) are boron delivery agents for boron neutron capture therapy (BNCT), a binary treatment modality for cancer. Presumably, these compounds accumulate selectively in tumor cells via intracellular trapping, which is mediated by hTK1. Favorable in vivo biodistribution profiles of 3CTAs led to promising results in preclinical BNCT of rats with intracerebral brain tumors. This review presents an overview on the design, synthesis, and biological evaluation of first- and second-generation 3CTAs. Boronated nucleosides developed prior to 3CTAs for BNCT and non-boronated N3-substituted thymidine conjugates for other areas of cancer therapy and imaging are also described. In addition, basic features of carborane clusters, which are used as boron moieties in the design and synthesis of 3CTAs, and the biological and structural features of TK1-like enzymes, which are the molecular targets of 3CTAs, are discussed.
摘要
3-卡硼烷胸苷类似物（3CTAs）是硼中子俘获治疗（BNCT）的硼供体药物，是一种用于癌症的二元治疗方式。推测这些化合物通过细胞内捕获选择性地在肿瘤细胞中积累，这是由 hTK1 介导的。3CTAs 的有利的体内生物分布特征导致了颅内脑肿瘤的大鼠临床前 BNCT 的有希望的结果。本综述介绍了第一代和第二代 3CTAs 的设计、合成和生物学评价。还描述了 BNCT 之前开发的硼核苷和用于其他癌症治疗和成像领域的非硼化 N3-取代胸苷缀合物。此外，还讨论了用作 3CTAs 设计和合成的硼部分的碳硼烷簇的基本特征，以及 3CTAs 的分子靶标 TK1 样酶的生物学和结构特征。
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