Design and synthesis of a DNA-crosslinking azinomycin analogues

Casely-Hayford, Maxwell A. and Pors, Klaus and James, Colin H. and Patterson, Laurence H. and Hartley, John A. and Searcey, Mark (2005) Design and synthesis of a DNA-crosslinking azinomycin analogues. Organic & Biomolecular Chemistry, 3 (19). pp. 3585-3589. ISSN 1477-0520. (The full text of this publication is not available from this repository)

The full text of this publication is not available from this repository. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1039/b508908e

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.

Item Type: Article
Projects: [52] 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: 01 May 2014 09:20
Resource URI: http://kar.kent.ac.uk/id/eprint/9305 (The current URI for this page, for reference purposes)
  • Depositors only (login required):