Design and synthesis of a DNA-crosslinking azinomycin analogue

Maxwell A. Casely-Hayford, Klaus Pors, Colin H. James, Laurence H. Patterson, John A. Hartley, Mark Searcey

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20 Citations (Scopus)


The azinomycins are potent antitumour that are able to crosslink DNA, but are relatively unstable and unlikely to progress as therapeutic candidates. A prototype analogue 4 with more clinical potential has been designed and synthesised and incorporates the epoxide function of the azinomycins and a nitrogen mustard. Two further analogues 5 and 6 that can alkylate DNA but cannot crosslink the duplex have also been synthesised. Compound 4 crosslinks DNA efficiently at nM concentrations. Compounds 4-6 were submitted to the NCI 60 cell line screen and have similar antitumour activity, although 4 is slightly less active than the non-crosslinking compounds. These observations will be important in the design of further azinomycin analogues with antitumour activity.
Original languageEnglish
Pages (from-to)3585-3589
Number of pages5
JournalOrganic & Biomolecular Chemistry
Issue number19
Early online date5 Sep 2005
Publication statusPublished - 2005

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