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[Mechanism of action and molecular design of hypoxic cell sensitizer].

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.