RSU 1069, a nitroimidazole containing an aziridine group. Bioreduction greatly increases cytotoxicity under hypoxic conditions.
RSU 1069, a nitroimidazole containing an aziridine group. Bioreduction greatly increases cytotoxicity under hypoxic conditions.
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RSU 1069，一种含有氮丙啶基团的硝基咪唑。
DOI：
10.1016/0006-2952(86)90566-6
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发表时间：
1986
影响因子：
5.8
通讯作者：
G. Adams
中科院分区：
文献类型：
--
作者：
I. Stratford;P. O'Neill;P. Sheldon;A. Silver;J. Walling;G. Adams
硝基杂环化合物的氧化还原性质已被确定为其生物学性质的重要决定因素[1，2]。单电子还原电位与硝基化合物作为低氧细胞的放射增敏剂的能力之间的相关性是开发可用作放射治疗中的放射增敏剂的药物的核心[3，4]。该系列中的一种先导化合物是米索硝唑（1-（2-硝基-1-咪唑基）-3-甲氧基-2-丙醇），尽管在达到其最大效果所需的剂量下具有神经毒性[5]，但已显示在某些临床情况下有益[6]。已经开发出比米索硝唑治疗率更高的药物，但其改善的疗效是基于较低的毒性和/或改善的肿瘤吸收[7，8]。RSU 1069（1-（2-硝基-1-咪唑基）-3-（1-氮丙啶基）-2-丙醇）在体外和体内都是比米索硝唑更有效的放射增敏剂[9，10]，尽管两种化合物具有相似的单电子氧化还原电位[9]。在结构上，RSU 1069与米索硝唑的不同之处在于氮丙啶取代了N1侧链中的甲氧基（图1）。氮丙啶是单官能烷基化剂，其可以与细胞大分子如DNA反应[11]。为了确定RSU 1069的异常高敏化效率的机制是否涉及氮丙啶基团的烷基化性质，已经在分子、细胞和体内水平上对该化合物的性质进行了研究。RSU 1069对缺氧细胞显示出非常高的毒性。本文综述了有关RSU的现有毒性数据
The red-ox properties of nitroheterocyclic compounds have been established as important determinants of their biological properties [1, 2]. The correlation between one-electron reduction potential and the ability of nitro compounds to act as radiosensitizers of hypoxic cells is central to the development of agents useful as adjuncts in radiotherapy [3, 4]. A lead compound in this series has been misonidazole (1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol), which, although neurotoxic at doses necessary to achieve its maximal effect [5], has been shown to be of benefit in some clinical situations [6]. Drugs of higher therapeutic ratio than misonidazole have been developed but their improved efficacy is based on lower toxicity and/or improved tumour uptake [7, 8]. RSU 1069 (1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol) is a substantially more efficient radiosensitizer than misonidazole both in vitro and in vivo [9, 10] even though both compounds have similar one-electron red-ox potentials [9].Structurally, RSU 1069 differs from misonidazole in that an aziridine replaces the methoxy group in the N1 side chain (Fig. 1). Aziridines are monofunctional alkylating agents which can react with cellular macromolecues such as DNA [11]. In order to establish whether the mechanism of the abnormally high sensitizing efficiency of RSU 1069 involves the alkylating properties of the aziridine group, studies have been carried out on the properties of this compound at the molecular, cellular and in vivo level. RSU 1069 shows very high toxicity towards hypoxic cells. This paper reviews the available toxicity data on RSU
SR-2508：2-硝基咪唑酰胺，临床使用的放射增敏剂应优于米索硝唑。
DOI：
10.1016/0360-3016(81)90460-0
发表时间：
1981
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
Brown,JM;Yu,NY;Brown,DM;Lee,WW
通讯作者：
Lee,WW
非蛋白质硫醇和细胞对药物和辐射的反应。
DOI：
10.1016/0360-3016(82)90720-9
发表时间：
1982
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
Biaglow,JE;Varnes,ME;Astor,M;Hall,EJ
通讯作者：
Hall,EJ