title: Substituent effect of a fluorine atom on the mutagenicity of nitroquinolines.
abstract: Some 16 nitroquinolines (NQs) and their fluorinated derivatives were tested for mutagenicity in Salmonella typhimurium TA100 without S9 mix to investigate the effect of fluorine-substitution on the mutagenicity. These NQs consist of 5-NQs, 5-nitroquinoline N-oxides (5-NQOs), N-methyl-5-nitroquinolinium methanesulfonates (N-Me-5-NQs) and 8-NQs, including three ortho-F-NQs, one meta-F-NQ, four para-F-NQs and four 3-F-NQs. For this purpose, eight F-NQs were newly synthesized. The data indicated that the ratio of the mutagenic activities (revertants/plate/nmol) of fluorinated NQs to those of the corresponding parent non-fluorinated compounds ranged from 0.6- to 119-fold. The fluorine atom located para to the nitro group markedly enhanced the mutagenicity (24-fold and more), while three ortho-fluorinated derivatives showed no significant increase in mutagenicity (enhancement ratio were 0.6, 0.8 and 1.7). With respect to 8-NQs, its meta-fluorinated derivative also had an enhanced mutagenicity over the parent compound (53-fold). In addition, although N-Me-5-NQ was less mutagenic than 5-NQ and 5-NQO, the mutagenicity of N-Me-5-NQ was most significantly enhanced by fluorine-substitution. These results suggest that introduction of a fluorine atom to the molecule in question may be a useful tool to modify their mutagenic potency and to better understand the mechanism of mutation.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan. saeki@phar.nagoya-cu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Saeki
authors.forename: R
authors.initials: R
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Kohara
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: Y
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: A
authors.initials: A
authors.lastname: Hakura
mesh_terms: D002850:Chromatography, Gel; D017611:Fluorine Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009600:Nitroquinolines / Q000138:chemical synthesis / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D017611:Fluorine Compounds; D009600:Nitroquinolines