Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation: The role of fluorene and fluorenone substituents as DNA intercalators.

N-Acyloxy-N-alkoxyamides are direct-acting mutagens in S. typhimurium TA100 and TA98. A reliable QSAR for their activity in TA100 has been developed, which indicates reversible intercalation into the DNA helix through naphthalene substituents.

Correction: Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator.

Correction for 'Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator' by Tony M. Banks, et al., Org.

Mutagenicity of N-acyloxy-N-alkoxyamides as an indicator of DNA intercalation part 1: evidence for naphthalene as a DNA intercalator.

N-Acyloxy-N-alkoxyamides are direct-acting mutagens in S. typhimurium TA100 with a linear dependence upon log P that maximises at log P0 = 6.4.

The effect of hydrophobicity upon the direct mutagenicity of N-acyloxy-N-alkoxyamides--Bilinear dependence upon LogP.

N-Acyloxy-N-alkoxyamides 1 are direct-acting mutagens for which a bilinear QSAR has been established, which predicts with accuracy their activity in the Ames reverse mutation assay in Salmonella typhimurium TA100, based upon their hydrophobicity (LogP), reactivity (pKA of the carboxylic acid of the N-carboxyl group) and TAFT steric parameters. From activity data for 55 congeners and incorporating five mutagens bearing long-chain hydrocarbons on the alkoxyl and acyloxyl groups, designed for this study, a maximal LogPo, is found to be LogP=6.4.

Steric effects on the direct mutagenicity of N-acyloxy-N-alkoxyamides-probes for drug-DNA interactions.

N-Acyloxy-N-alkoxyamides (see structure 1, below) are direct-acting mutagens for which a QSAR has been established that predicts with accuracy their activity in the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium TA100. Steric bulk next to oxygen on the alkoxyl side-chain in structure 4 has no impact on activity, but branching at the position adjacent (alpha) to the ester-carbonyl of the leaving group in structure 5 strongly inhibits mutagenicity. Both results reflect the manner in which these molecules interact with DNA.