Casely-Hayford, Maxwell A. and Pors, K. and James, C.H. and Patterson, L.H. and Hartley, J.A. and Searcey, M. (2005) Design and synthesis of a DNA-crosslinking azinomycin analogues. Organic and Biomolecular Chemistry, 3 (19). pp. 3585-3589. ISSN 1477-0520 .
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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.
|Projects:|| Development of DNA-crosslinking anticancer agents|
|Uncontrolled keywords:||antitumour antibiotics; sequence selectivity; carzinophilin; cytotoxicity; alkylation; naphthoate; mechanism; cleavage; agent|
|Subjects:||Q Science > QD Chemistry|
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Maxwell Casely-Hayford|
|Date Deposited:||15 Sep 2008 21:40|
|Last Modified:||13 Jun 2012 09:49|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/9305 (The current URI for this page, for reference purposes)|
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