Abstract

Our understanding of the chemistry and biology of the enediyne class of antitumor antibiotics is still developing and
faces further challenges. The cleavage of double-stranded DNA through hydrogen abstraction by enediyne-derived
radicals is a generally well-accepted mechanism. However, the mechanisms of several unexpected and complex
cytotoxic effects of enediynes,such as RNA and protein damage or the generation of p-quinone species, have yet to be fully elucidated. Despite several carefully crafted experimental and theoretical studies on simplified systems,the
behavior of the major chemical perpetrators of such cytotoxicity, namely the biradical intermediates formed by natural enediynes, remains more a matter of conjecture than a point of fact.