Abstract
Development of radiosensitizers has focused on organic compounds, for the most part, nitroimidazoles. The relationship of the efficiency of sensitization to E 1–2 was noted for nitroimidazoles during structure/activity studies1. However, changing the reduction potential to increase sensitizing efficiency is impractical beyond a certain point due to the accompanying toxicity2. This toxicity, which is more pronounced in hypoxic cells3, is due to metabolic reduction of the nitroaromatic group (e.g. Rauth4). Considerable attention has been given to both exploiting this selective toxicity as described in this volume (chemosensitization, hypoxic cytotoxins and markers for hypoxia) and to minimizing the toxicity which results in side-effects. Complexes of certain metals may offer some advantages because of their redox properties, thiol reactivity and DNA binding properties, as previously summarized5,6. DNA binding may itself lead to an interaction with ionizing radiation, and DNA binding metals may be used to target nitroaromatics to DNA. Alternatively, certain transition metals (e.g. Fe, Co, Ni, Cu) surrounded by suitable ligands may have reduction potentials in the appropriate range.
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Skov, K.A. (1990). Toxicity of Metal Complexes with Radiosensitizing Properties. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_24
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