Dual stimulatory and inhibitory effects of fluorine-substitution on mutagenicity: an extension of the enamine epoxide theory for activation of the quinoline nucleus.
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.
Saeki
K
K
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Kawai
H
H
Kawazoe
Y
Y
Hakura
A
A
D001564:Benzo(a)pyrene / Q000737:chemistry / Q000633:toxicity; D004852:Epoxy Compounds / Q000737:chemistry / Q000633:toxicity*; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010618:Phenanthrolines / Q000737:chemistry / Q000633:toxicity; D011804:Quinolines / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics; D013329:Structure-Activity Relationship
D004852:Epoxy Compounds; D009153:Mutagens; D010618:Phenanthrolines; D011804:Quinolines; D001564:Benzo(a)pyrene