Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides — the role of electrophilic nitrogen

Tony M. Banks; Antonio M. Bonin; Stephen A. Glover; Arungundrum S. Prakash

doi:10.1039/B301618H

Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides — the role of electrophilic nitrogen

Tony M. Banks,^a Antonio M. Bonin,^b Stephen A. Glover^a and Arungundrum S. Prakash^c

^a Division of Chemistry, School of Biological, Biomedical and Molecular Sciences, University of New England, Armidale 2351, Australia

^b School of Chemistry, University of Sydney, Australia

^c National Research Centre for Environmental Toxicology, University of Queensland, 39 Kessels Rd., Coopers Plains, Australia

Abstract

N-Acyloxy-N-alkoxyamides are anomeric amides that are direct-acting mutagens. They have been shown to damage DNA in the major and the minor grooves in a pH and sequence-selective manner. In acidic media, they damage adenines at N3 in the minor groove but above neutral pH, only guanine is damaged at N7 in the major groove. Both the acyloxy leaving group and the alkoxy group at the amide nitrogen are responsible for their electrophilicity and Salmonella mutagenicities in TA100 and DNA damage data confirm that the mutagens react with DNA in an intact form, rather than by solvolysis to electrophilic nitrenium ions in the cytosol, or in vitro, prior to reacting with DNA. Hydrophobicity plays a role in both mutagenicity and DNA damage.

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Publication details

The article was received on 10 Feb 2003, accepted on 16 May 2003 and first published on 02 Jun 2003

Article type: Paper

DOI: 10.1039/B301618H

Citation: Org. Biomol. Chem., 2003,1, 2238-2246

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Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides — the role of electrophilic nitrogen

T. M. Banks, A. M. Bonin, S. A. Glover and A. S. Prakash, Org. Biomol. Chem., 2003, 1, 2238
DOI: 10.1039/B301618H
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Organic & Biomolecular Chemistry

Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides — the role of electrophilic nitrogen

Abstract

Supplementary files

Publication details

Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides — the role of electrophilic nitrogen

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