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Design and synthesis of a DNA-crosslinking azinomycin analogues

Casely-Hayford, Maxwell A., Pors, Klaus, James, Colin H., Patterson, Laurence H., Hartley, John A., Searcey, Mark (2005) Design and synthesis of a DNA-crosslinking azinomycin analogues. Organic & Biomolecular Chemistry, 3 (19). pp. 3585-3589. ISSN 1477-0520. (doi:10.1039/b508908e) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:9305)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
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
DOI/Identification number: 10.1039/b508908e
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: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Engineering and Physical Sciences Research Council (https://ror.org/0439y7842)
University College London (https://ror.org/02jx3x895)
Depositing User: Maxwell Casely-Hayford
Date Deposited: 15 Sep 2008 21:40 UTC
Last Modified: 12 Jul 2022 10:38 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/9305 (The current URI for this page, for reference purposes)

University of Kent Author Information

Casely-Hayford, Maxwell A..

Creator's ORCID: https://orcid.org/0000-0003-4054-4371
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