Mutagenic decomposition products of nitrosated 4-chloroindoles

Abstract

4-Chloro-6-methoxyindole, a constituent of fava beans, forms a potent direct-acting mutagen, 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime, when nitrosated. In order to better understand the properties of this mutagen, we have studied a readily-available analog, 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, prepared by nitrosation of 4-chloroindole. This analog is also mutagenic, and both mutagens decompose rapidly at neutral or higher pH to yield in each case a new, less potent mutagen which then reacts further to form a nonmutagenic final product. The two products arising from 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, on the basis of comparison of spectroscopic and chromatographic evidence with that from authentic standards, are 4-chloro-N-nitrosodioxindole and 4-chloroisatin; those arising from 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime appear to be the corresponding 6-methoxy analogs. The interplay of these pathways with respect to net biological activity, especially under gastric conditions, remains to be described.