Nishimoto S, Kagiya T
Dept. of Hydrocarbon Chemistry, Faculty of Engineering, Kyoto Univ.
Gan No Rinsho. 1988 Oct;34(13):1853-8.
Fluorine modification of nitroazoles has been characterized as a useful method of molecular design of hypoxic cell sensitizers. In vitro sensitizing activities were correlated to the promotion efficiency of radiolytic hydroxylation of thymine to thymine glycol and to the one-electron reduction potential of a variety of fluorinated and non-fluorinated nitroazole derivatives. The absolute activity of sensitizers, which was evaluated from the enhancement ratio in vivo (SERvivo) and the tumor affinity, showed a linear relationship with the in vitro sensitizing activity. The sensitizer dose required to achieve an SERvivo of 1.5 decreased as the tumor affinity became greater. The fluorine modification of nitroazole sensitizers could enhance both the absolute activity and the tumor affinity.
硝基唑的氟修饰已被视为一种用于缺氧细胞增敏剂分子设计的有效方法。体外增敏活性与胸腺嘧啶辐射分解羟基化生成胸腺嘧啶二醇的促进效率以及多种氟化和非氟化硝基唑衍生物的单电子还原电位相关。从体内增强比（SERvivo）和肿瘤亲和力评估的增敏剂绝对活性与体外增敏活性呈线性关系。随着肿瘤亲和力增加，达到SERvivo为1.5所需的增敏剂剂量降低。硝基唑增敏剂的氟修饰可同时提高绝对活性和肿瘤亲和力。
