期刊
AUSTRALIAN JOURNAL OF CHEMISTRY
卷 76, 期 1, 页码 1-24出版社
CSIRO PUBLISHING
DOI: 10.1071/CH22205
关键词
acyloxy alkoxyamides; ames mutagenicity; anomeric amides; bilinear QSAR; deamination; direct-acting mutagenicity; DNA binding; groove binding; HERON reactions; intercalation; linear QSAR; mutagenic amides; nitrogen deletion; PAH; pyramidal amides; QSAR; quantitative structure-activity; relationship; skeletal editing; TA98; TA100
This account describes the origins of research on the mutagenicity of N-acyloxy-N-alkoxyamides. The study focuses on their ability to mutate DNA in the Ames reverse mutation assay without the need for metabolic activation. The impact of structural variation on cellular access to, binding to, and reactivity with DNA is explored, with emphasis on hydrophobicity, electrophilic reactivity, steric effects, and intercalation.
This account describes the origins of our extensive investigations into the mutagenicity of N-acyloxy-N-alkoxyamides. Since their discovery as biologically active anomeric amides that mutate DNA in the Ames reverse mutation assay without the need for metabolic activation, we have used activities in the Ames test to understand the impact of structural variation on cellular access to, binding to and reactivity with DNA. We have developed an understanding of the roles played by hydrophobicity, electrophilic reactivity, steric effects and, importantly, intercalation on mutagenicity levels and therefore interactions with DNA. The evolution and application of meaningful quantitative structure-activity relationships is described, and examples of their utility in explaining molecule-DNA interactions are given. Their ability to explain previous mutagenicity data and, importantly, to predict meaningful mutagenic behaviour is also demonstrated.
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