Abstract
Bioreductive agents are thought to act in vivo and in vitro through their activation upon enzymatic one-electron reduction to produce metabolites1 which are considerably more cytotoxic than the parent compound. Such bioreduction is critically dependant upon such factors as oxygen tension, the redox potential of the agent and temperature, the latter reflecting the enzymatic steps. Oxygen acts by protecting against formation of reduced metabolites of the agents through ‘futile cycling’ a process which generates superoxide at the expense of the one-electron reduced intermediate of the bioreductive agent. Therefore their preferential cytotoxicity towards hypoxic cells is as a consequence of the protective role of oxygen under aerobic conditions. Agents which exhibit such bioreductive properties may have potential application as chemotherapeutic agents of hypoxic cells commonly found in tumours. Agents which have been demonstrated to show enhanced toxicity towards hypoxic cells compared with aerobic cells include nitroimidazoles1, quinones2 and benzotriazine di-N-oxides3.
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O’Neill, P., Jenner, T.J., Sapora, O., Crump, P.W., Cunniffe, S.M.T., Fielden, E.M. (1990). The Role of DNA Damage in the Bioreductive Action of 2-Nitroimidazoles. 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_5
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DOI: https://doi.org/10.1007/978-1-4615-3768-7_5
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