Nitron derivatives to Blatter radicals: novel anti-cancer pro-drugs and mechanistic probes

布拉特自由基的硝基衍生物：新型抗癌前药和机制探针

• 批准号: 2214221
• 金额: --
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2214221
• 关键词: Nitron; derivatives; Blatter; radicals; novel

New, selective cancer treatments continue to be a major focus of the pharmaceutical and other life science industries. We will harness a recently-discovered facile reaction of the simple heterocycle Nitron to give isolable benzotriazinyl ('Blatter') radicals, which have been implicated as cytotoxic DNA-damaging species in the mechanism of action of Tirapazamine (a selective cancer drug currently in clinical trials). The direct biological evaluation of a broad range of novel Blatter radicals will provide a previously unexplored, unique mechanistic probe of the origin of tirapazamine cytotoxicity. In addition, Nitron and synthetic derivatives will be explored as alternative pro-drugs to tirapazamine for in situ access to benzotriazinyl species.

新的、选择性的癌症治疗继续是制药和其他生命科学行业的主要焦点。我们将利用最近发现的简单杂环硝基的简单反应来产生可分离的苯并三氮基(布拉特)自由基，这些自由基已被认为是替帕西明(一种目前正在临床试验的选择性抗癌药物)的作用机制中涉及的细胞毒性DNA损伤物种。对一系列新的布拉特自由基的直接生物学评价将为梯帕拉明细胞毒性的起源提供一个以前从未探索过的独特的机制探针。此外，还将探索硝基和合成衍生物作为替拉帕拉明的替代药物，以实现苯并三嗪物种的原位访问。