Investigation of the molecular reactivity of bioactive oxiranylmethyloxy anthraquinones

The design of a multitarget and multifunctional small molecule containing twofunctional groups reacting through different mechanisms represents an attractivegoal for the medicinal chemist. The preparation of two bifunctional oxiranylmethyloxyanthraquinones, previously investigated as anticancer agents, is described here.These compounds combine a planar, DNA‐intercalating and pro‐oxidant anthraqui-none scaffold and the alkylating epoxide functions which can covalently react withthe nucleic acid. Their multilevel molecular reactivity was studied through acombination of analytical techniques: The DNA‐binding properties were investigatedusing a mass spectrometry‐based binding assay and by nuclear magnetic resonance,highlighting the formation of a covalent adduct with a nucleobase. Moreover, thecontribution of the pro‐oxidant redox cycling was evaluated.