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Mutagenicity and DNA damage studies of N-acyloxy-N-alkoxyamides ? the role of electrophilic nitrogenElectronic supplementary information (ESI) available: a partial sequence of the pBR322 DNA, solvolysis rate constants and primary bimolecular rate constants. See http://www.rsc.org/suppdata/ob/b3/b301618h/

2003; Royal Society of Chemistry; Volume: 1; Issue: 13 Linguagem: Inglês

10.1039/b301618h

1477-0539

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

Cancer therapeutics and mechanisms

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.