Nitroarene radiosensitizers

The reduction potentials of metronidazole, nimorazole, misonidazole, and nitrofurantoin (Figure 1, 8, 9, 10 and 11 respectively) and analogues of these nitroarene radiosensitizers were thus measured and compared with the concentrations C of the compounds needed to achieve a defined radiosensitizing effect in mammalian cells. QSARs of the form ... 

Redox-controlled reactions of nitroarene radiosensitizers in chemical systems... 

Figure 2. Relationship between efficiency in radiosensitizing hypoxic mammalian cells in vitro and the reduction potential of nitroarenes. Data from [88].

Reactions of nitroarenes with both sugar and base radicals have been studied in some depth by several groups, summarized in earlier reviews [77-79,93,100]. Thus a radical that clearly forms adducts, such as that derived from an ether, reacted with nitroimidazoles with a redox relationship three times shallower than observed for radiosensitization of mammalian cells [100] ... 

The redox dependence of hydrogen abstraction from sugars by base/nitro-arene radical-adducts (nitroxyl radicals) in DNA has not yet been characterized, and it is quite possible that nitroarenes form adducts at both base and sugar sites. A detailed molecular understanding of the mechanisms of radiosensitization of hypoxic cells therefore remains elusive. For a complete picture it will be necessary to include an appreciation of the structure and accessibility of the target sites. 

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