A Proposal for the Mechanism-of-Action of Diazoparaquinone Natural Products

摘要

The diazoparaquinone family of antibiotics,exemplified by the naturally occurring species prekinamycin (la),kinamycin F (2),and lomaiviticin A (3),has had a long and storied history,featuring two major structural revisions (N-cyanocarbazole -> diazofluorene for the kinamycins,and diazobenzo[b]fluorene ->diazobenz[a]-fluorene for isoprekinamycin (not shown)).Following these corrections,two mechanism-of-action hypotheses have been proposed.Jebaratnam,using diazofluorene as a model system,suggested that oxidative activation of the diazo function might lead to DNA damaging reactive oxygen species via a putative C(ll) radical.