The formation and metabolism of N-hydroxymethyl compounds--IX. N-(acetoxymethyl)-4-chlorobenzamide: an electrophile but not a mutagen in Salmonella typhimurium.
作者： Mark Overton , Michael D Threadgill , James K Chipman , Andreas Gescher , John A Hickman
DOI: 10.1016/0006-2952(86)90690-8
关键词:
摘要: Abstract The electrophilic properties of 4-chloro- N -(hydroxymethyl) benzamide as a model compound carbinolamides formed during the metabolic oxidation -methylamides were investigated. 4-Cholo- -(hydroxymethyl)benzamide did not react with nucleophiles such cyanide or glutathione under physiological conditions. In contrast, -(acetoxymethyl)-4-chlorobenzamide yielded cyanomethylamide KCN and S -(chlorobenzamidomethyl) glutathione. Under non-aqueous conditions, reacted ethanethiol, methanol diethylamine in presence base, whereas afford products these These results show clearly that is precursor reactive methyleneimines. 4-Chloro- was biotransformed to species when incubated mouse hepatic microsomes microsomal supernatant acetyl-CoA PAPS generating system. Neither nor its acetate ester mutagenic short term bacterial assay using Salmonella typhimurium . Nevertheless, esters carbinolamides, -(acetoxymethyl)-4-chlorobenzamide, might possess toxic carcinogenic properties.
elsevier.com
sci-hub.se 参考文章(13)
David Ross, Peter B. Farmer, Andreas Gescher, John A. Hickman, Michael D. Threadgill, The formation and metabolism of N-hydroxymethyl compounds—I: The oxidative N-demethylation of N-dimethyl derivatives of arylamines, aryltriazenes, arylformamidines and arylureas including the herbicide monuron Biochemical Pharmacology. ,vol. 31, pp. 3621- 3627 ,(1983) , 10.1016/0006-2952(82)90585-8
TAKEO UEDA, YOSHIHISA OKAMOTO, TADAKAZU TSUJI, MASAKO MURAOKA, Syntheses of 2-acylaminoacetamidine and 3-acylaminopropionamidine derivatives. Chemical & Pharmaceutical Bulletin. ,vol. 16, pp. 2355- 2361 ,(1968) , 10.1248/CPB.16.2355
David Ross, Peter B. Farmer, Andreas Gescher, John A. Hickman, Michael D. Threadgill, The formation and metabolism of N-hydroxymethyl compounds--III. The metabolic conversion of N-methyl and N,N,-dimethylbenzamides to N-hydroxymethyl compounds. Biochemical Pharmacology. ,vol. 32, pp. 1773- 1781 ,(1983) , 10.1016/0006-2952(83)90124-7
J.P. Seiler, Herbicidal phenylalkylureas as possible mutagens Pesticide Biochemistry and Physiology. ,vol. 12, pp. 183- 190 ,(1979) , 10.1016/0048-3575(79)90083-X
Michael J. Gidley, Jermy K.M. Sanders, Evelyn R. Myers, Michael C. Allwood, The mode of antibacterial action of some ‘masked’ formaldehyde compounds FEBS Letters. ,vol. 127, pp. 228- 232 ,(1981) , 10.1016/0014-5793(81)80211-6
Mark Overton, John A. Hickman, Michael D. Threadgill, Keith Vaughan, Andreas Gescher, The generation of potentially toxic, reactive iminium ions from the oxidative metabolism of xenobiotic N-alkyl compounds. Biochemical Pharmacology. ,vol. 34, pp. 2055- 2061 ,(1985) , 10.1016/0006-2952(85)90394-6
Dorothy M. Maron, Bruce N. Ames, REVISED METHODS FOR THE SALMONELLA MUTAGENICITY TEST Mutation Research. ,vol. 113, pp. 173- 215 ,(1983) , 10.1016/0165-1161(83)90010-9
John Ashby, C.R. Richardson, P.A. Lefevre, R.D. Callander, J.A. Styles, Chloracetamide-N-metholol: an example of an in vitro and in vivo clastogen which is non-mutagenic to Salmonella. Mutation Research\/genetic Toxicology. ,vol. 156, pp. 19- 32 ,(1985) , 10.1016/0165-1218(85)90003-5
C.J. Logan, F.H. Cottee, J.A. Page, The formation of a novel mercapturic acid during the metabolism of an N-methyl aromatic amine, 4-cyano-N,N-dimethylanine Biochemical Pharmacology. ,vol. 33, pp. 2345- 2346 ,(1984) , 10.1016/0006-2952(84)90680-4
Sally J. Addison, Bernadette D. M. Cunningham, E. Nicholas Gate, Prakash Z. Shah, Michael D. Threadgill, The formation and metabolism of N-hydroxymethyl compounds. Part 6. The synthesis of S-amidomethyl-, S-ureidomethyl-, and S-(1,3,5-triazin-2-ylaminomethyl)-glutathione derivatives Journal of The Chemical Society-perkin Transactions 1. ,vol. 16, pp. 75- 79 ,(1985) , 10.1039/P19850000075