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|Title:||The Role of Steric Effects in the Direct Mutagenicity of N-acyloxy-N-alkoxyamides||Contributor(s):||Andrews, L (author); Bonin, AM (author); Fransson, LE (author); Gillson, A (author); Glover, S (author)||Publication Date:||2006||DOI:||10.1016/j.mrgentox.2006.02.003||Handle Link:||https://hdl.handle.net/1959.11/39||Abstract:||Electrophilic N-acyloxy-N-alkoxyamides are mutagenic in Salmonella typhimurium TA100 without the need for S9 metabolic activation and they react with DNA at guanine N7 at physiological pH. Since these are direct-acting mutagens, structural factors influence binding and reactivity with DNA. Mutagenicity in TA100 can be predicted by a QSAR incorporating hydrophobicity (log P), stability to substitution reactions at nitrogen (pKa of the leaving acid) and steric effects of para-aryl substituents (Es). A number of mutagens exhibit activities that deviate markedly from the predicted values and they fall into two classes: di-tert-butylated N-benzoyloxy-N-benzyloxybenzamides, which because of their size are most probably excluded from the major groove or are unable to achieve a transition state for reaction with DNA, and N-benzoyloxy-N-butoxyalkylamides with branching -to the amide carbonyl, which are resistant to SN2 reactions at the amide nitrogen.||Publication Type:||Journal Article||Source of Publication:||Mutation Research: Genetic Toxicology and Environmental Mutagens, 605(1-2), p. 51-62||Publisher:||Elsevier Science BV||Place of Publication:||Netherlands||ISSN:||1383-5718||Field of Research (FOR):||030401 Biologically Active Molecules||Peer Reviewed:||Yes||HERDC Category Description:||C1 Refereed Article in a Scholarly Journal||Statistics to Oct 2018:||Visitors: 224
|Appears in Collections:||Journal Article|
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