Nitron derivatives to Blatter radicals: novel anti-cancer pro-drugs and mechanistic probes

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New, selective cancer treatments continue to be a major focus of the pharmaceutical and other life science industries. We will harness a recently-discovered facile reaction of the simple heterocycle Nitron to give isolable benzotriazinyl ('Blatter') radicals, which have been implicated as cytotoxic DNA-damaging species in the mechanism of action of Tirapazamine (a selective cancer drug currently in clinical trials). The direct biological evaluation of a broad range of novel Blatter radicals will provide a previously unexplored, unique mechanistic probe of the origin of tirapazamine cytotoxicity. In addition, Nitron and synthetic derivatives will be explored as alternative pro-drugs to tirapazamine for in situ access to benzotriazinyl species.