Dual Stimulatory and Inhibitory Effects of Fluorine-Substitution on Mutagenicity : An Extension of the Enamine Epoxide Theory for Axtivation of the Quinoline Nucleus

Abstract

Nineteen mono- and di-fluorinated derivatives of quinoline, 1, 7-phenanthroline, 1, 10-phenanthroline, benzo-[h]quinoline, and benzo[f]quinoline were subjected to analysis of their structure-mutagenicity relationships. For this purpose, six new fluorinated derivatives were synthesized. The results support that the enamine epoxide structure of the pyridine moiety, as well as the bay-region epoxide structure, is responsible for mutagenicity. Formation of K-region epoxides might involve a detoxification process rather than mutagenic activation.