Summary
1. Rat liver microsomes catalize N4-hydroxylation of sulfanilamide in the presence of NADPH and O2.
2. p-Hydroxylaminobenzenesulfonamide was isolated and identified by means of thin layer chromatography.
3. Human liver microsomes have been found to be equally effective.
4. In concentrations comparable to therapeutic blood levels only p-hydroxylaminobenzenesulfonamide and p-nitrosobenzenesulfonamide produce methaemoglobin. Other possible metabolites including 3-hydroxysulfanilamide were ineffective in these concentrations.
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Literatur
Bauer, H., and S. M. Rosenthal: 4-Hydroxylaminobenzenesulfonamide, its acetyl derivatives and diazotization reaction. J. Amer. chem. Soc. 66, 611 (1944).
Bodansky, O.: Methemoglobinemia and methemoglobin-producing compounds. Pharmacol. Rev. 3, 144 (1951).
Bratton, A. C., H. J. White, and E. K. Marshall Jr.: Comparison of certain pharmacological and antibacterial properties of p-hydroxylaminobenzenesulfonamide and sulfanilamide. Proc. Soc. exp. Biol. (N.Y.) 42, 847 (1939).
Friederiszick, K. F., u. W. Toussaint: Nebenwirkungen eines modernen „Langzeitsulfonamids“ bei therapeutischer Anwendung im Säuglingsalter. Med. Klin. 55 (II), 459 (1960).
Gatterman-Wieland: Die Praxis des organischen Chemikers, S. 158. Berlin: W. de Gruyter 1962.
Gibberd, G. F.: Prontosil and similar compounds in the treatment of puerperal hemolytic streptococcus infections. Brit. med. J. 1937 II, 695.
Heubner, W.: Methämoglobinbildende Gifte. Ergebn. Physiol. 43, 9 (1940).
James, G. V.: The isolation of some oxidation products of sulphanilamide from urine. Biochem. J. 34, 640 (1940).
Kiese, M.: Oxydation von Anilin zu Nitrosobenzol im Hunde. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 235, 354 (1959).
D. Reinwein u. H. D. Waller: Die Hämiglobinbildung durch Phenylhydroxylamin und Nitrosobenzol in roten Zellen in vitro. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 210, 393 (1950).
, u. H. Uehleke: Der Ort der N-Oxydation des Anilins im höheren Tier. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 242, 117 (1961).
Mayer, R. L.: Recherches sur le mécanisme de l'action antistreptococcique de l'aminobenzènesulfamide et de ses dérivés. Bull. Acad. Méd. (Paris) 117, 727 (1937).
Paton, J. P. J., and J. C. Eaton: Sulfhaemoglobinemia and methaemoglobinemia following administration of p-aminobenzene sulfonamide. Lancet 1937 I, 1159.
Shinn, L. E., E. R. Main, and R. R. Mellon: Conversion of sulfanilamide into p-hydroxyalamino-benzene-sulfonamide by ultraviolet irradiation. Proc. Soc. exp. Biol. (N.Y.) 42, 736 (1939).
Stöffler, G., R. K. Thauer u. H. Uehleke: Methämoglobinbildung durch p-Hydroxylaminobenzolsulfonamid in Nabelschnur- und Erwachsenenerythrocyten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 251, 196 (1965).
Thorpe, W. V., and R. T. Williams: Studies in detoxication. The synthesis of some possible biological oxidation products of sulphanilamide. Biochem. J. 35, 61 (1941).
Thorpe, W. V., R. T. Williams, and in part J. Shelswell: Studies in detoxication. On the alleged formation of p-hydroxylaminobenzenesulphonamide and p-aminophenole from sulphanilamide in vivo, on the colour reactions used for their detection, and on the possible formation of aminophenolsulphonamides. Biochem. J. 35, 52 (1941).
Uehleke, H.: On the mechanism of enzymatic oxidation of aromatic amines and N-alkylanilines by liver microsomes. V. Internat. Kongr. Biochem., Moskau, August 1961. Abstr. S. 399. London: Pergamon Press 1961a.
Relations between structure, velocity of biological N-hydroxylation and toxicity of aromatic amines, in Brodie, B. B., and E. G. Erdös: eds Metabolic factors controlling duration of drug action. First Intern. Pharmacol. Meeting, Stockholm 1961b, Vol. 6, p. 31. London: Pergamon Press 1962.
Williams, R. T.: The metabolism of sulphonamides. The isolation and identification of 3-hydroxysulphanilamide as the oxidation product of sulphanilamide in the rabbit. Biochem. J. 40, 219 (1946).
The metabolism of sulphonamides. The detection of 3-hydroxysulphanilamide in the urine of hospital patients treated with sulphanilamide. Biochem. J. 41, 1 (1947).
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Referat der 28. Tagung der Deutschen Pharmakologischen Gesellschaft vom 5.–8. Oktober 1964 in Bad Nauheim: Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 250, 286 (1965).
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Thauer, R.K., Stöffler, G. & Uehleke, H. N-Hydroxylierung von Sulfanilamid zu p-Hydroxylaminobenzolsulfonamid durch Lebermikrosomen. Naunyn - Schmiedebergs Arch 252, 32–42 (1965). https://doi.org/10.1007/BF00246427
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DOI: https://doi.org/10.1007/BF00246427