Brown N K, Nguyen T T, Taghizadeh K, Wishnok J S, Tannenbaum S R
Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139.
Chem Res Toxicol. 1992 Nov-Dec;5(6):797-801. doi: 10.1021/tx00030a011.
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.
4-氯-6-甲氧基吲哚是蚕豆的一种成分，经亚硝化后会形成一种强效的直接作用诱变剂4-氯-6-甲氧基-2-羟基-1-亚硝基吲哚啉-3-酮肟。为了更好地了解这种诱变剂的性质，我们研究了一种易于获得的类似物4-氯-2-羟基-1-亚硝基吲哚啉-3-酮肟，它是通过对4-氯吲哚进行亚硝化制备的。这种类似物也具有诱变作用，并且这两种诱变剂在中性或更高pH值下都会迅速分解，每种情况下都会产生一种新的、活性较低的诱变剂，然后进一步反应形成一种无诱变活性的最终产物。根据光谱和色谱证据与标准品的比较，4-氯-2-羟基-1-亚硝基吲哚啉-3-酮肟产生的两种产物是4-氯-N-亚硝基二氢吲哚和4-氯异吲哚酮；4-氯-6-甲氧基-2-羟基-1-亚硝基吲哚啉-3-酮肟产生的产物似乎是相应的6-甲氧基类似物。这些途径在净生物活性方面的相互作用，尤其是在胃部条件下，仍有待描述。
