This is not the latest version of this item. The latest version can be found here.
Design and synthesis of a DNA-crosslinking azinomycin analogue
Pors, Klaus Casely-Hayford, M.A. Hartley, J.A. Patterson, Laurence H. Searcey, M.
Pors, Klaus
Casely-Hayford, M.A.
Hartley, J.A.
Patterson, Laurence H.
Searcey, M.
Publication Date
2005
End of Embargo
Supervisor
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
The azinomycins are potent antitumour antibiotics 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.
Version
No full-text in the repository
Citation
Pors, K., Casely-Hayford, M., Hartley, J.A. and Patterson, L.H. (2005). Design and synthesis of a DNA-crosslinking azinomycin analogue. Organic & Biomolecular Chemistry. Vol. 3, No. 19, pp. 3585-3589.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article