Effects of oligofluorine substitution on the mutagenicity of quinoline: a study with twelve fluoroquinoline derivatives

A total of 12 variously fluorinated derivatives of quinoline (Q) were teste d for their mutagenicity in Salmonella typhimurium TA100 in the presence of S9 mix to investigate the structure-mutagenicity relationship in oligofluo rinated quinolines. Nine of them, 3,7-di-, 5,6-di-, 6,7-di-, 6,8-di-, 7,8-d i-, 3,5,7-tri-, 5,6,8-tri-, 6,7,8-tri-, and 5,6,7,8-tetrafluoroquinolines ( FQs), were newly synthesized for this purpose. Those fluorinated at positio n 3 were all non-mutagenic. Mutagenicity was enhanced by fluorine-substitut ion at position 5 or 7, but not in 3-FQs (i.e., 3,5-di-, 3,7-di-, and 3,5,7 -triFQs). Some of the 6-fluorinated derivatives showed less maximum induced -revertants with more mutagenic potencies in terms of induced-revertants pe r dose than quinoline. No marked change occurred by fluorine-substitution a t position 8. These results show that the effect of di- and trifluoro-subst itution on mutagenicity is generally additive, while that of tetrafluorinat ion approaches the deactivating effect of perfluorination. Our study sugges ts that 3-fluorine-substitution in the pyridine moiety may be a useful mean s of antimutagenic structural modification in pyridine-fused aromatic chemi cals for medicinal and agricultural use. (C) 1999 Elsevier Science B.V. All rights reserved.