C. Denis Mee

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Formaldehyde was examined for bacterial mutagenicity using Escherichia coli WP2(pKM101) and WP2uvrA(pKM101), and Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102, in the absence of any exogenous source of metabolic activation. Using pre-incubation exposure, clear mutagenicity was seen for TA98, TA100 and TA102, and both E. coli strains.(More)
Aromatic and heteroaromatic amines (ArNH(2)) represent a class of potential mutagens that after being metabolically activated covalently modify DNA. Activation of ArNH(2) in many cases starts with N-hydroxylation by P450 enzymes, primarily CYP1A2. Poor understanding of structure-mutagenicity relationships of ArNH(2) limits their use in drug discovery(More)
Primary aromatic and heteroaromatic amines are notoriously known as potential mutagens and carcinogens. The major event of the mechanism of their mutagenicity is N-hydroxylation by P450 enzymes, primarily P450 1A2 (CYP1A2), which leads to the formation of nitrenium ions that covalently modify nucleobases of DNA. Energy profiles of the NH bond activation(More)
The metabolism of aromatic and heteroaromatic amines (ArNH₂) results in nitrenium ions (ArNH⁺) that modify nucleobases of DNA, primarily deoxyguanosine (dG), by forming dG-C8 adducts. The activated amine nitrogen in ArNH⁺ reacts with the C8 of dG, which gives rise to mutations in DNA. For the most mutagenic ArNH₂, including the majority of known genotoxic(More)
The hypothesis that antagonists of the neuropeptide Y5 receptor would provide safe and effective appetite suppressants for the treatment of obesity has prompted vigorous research to identify suitable compounds. We discovered a series of acylated aminocarbazole derivatives (e.g., 3a) that are potent and selective Y5 antagonists, representing interesting(More)
Boronic acids and their esters are important building blocks in organic syntheses including those for drug substances and for which, as far as it can be determined, there are no published reports of testing for genotoxicity. A number of boronic acids have now been tested in this laboratory using Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100(More)
We describe how we have been able to design 4-aminobiphenyls that are nonmutagenic (inactive in the Ames test). No such 4-aminobiphenyls were known to us, but insights provided by quantum mechanical calculations have permitted us to design and synthesize some examples. Importantly, the quantum mechanical calculations could be combined with predictions of(More)
Recent problems with the supply of Difco bacto agar have forced some laboratories to evaluate alternative agars for use in the Salmonella/microsome assay. This led to the independent observation in two laboratories (Boots and Glaxo) that Salmonella typhimurium TA97a is sensitive to certain types of agar that may be used to prepare Vogel-Bonner minimal(More)
A computational method for predicting the likelihood of aromatic amines being active in the Ames test for mutagenicity was trialed on a set of aminopyrazoles. A virtual array of compounds was generated from the available sets of hydrazines and α-cyanoaldehydes (or ketones) and quantum mechanical calculations used to compute a probability of being active in(More)
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