Kato T, Saeki K, Kawazoe Y, Hakura A
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
Mutat Res. 1999 Feb 19;439(2):149-57. doi: 10.1016/s1383-5718(98)00188-0.
A total of 12 variously fluorinated derivatives of quinoline (Q) were tested for their mutagenicity in Salmonella typhimurium TA100 in the presence of S9 mix to investigate the structure-mutagenicity relationship in oligofluorinated quinolines. Nine of them, 3,7-di-, 5,6-di-, 6,7-di-, 6,8-di-, 7,8-di-, 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 position 3 were all non-mutagenic. Mutagenicity was enhanced by fluorine-substitution 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 per dose than quinoline. No marked change occurred by fluorine-substitution at position 8. These results show that the effect of di- and trifluoro-substitution on mutagenicity is generally additive, while that of tetrafluorination approaches the deactivating effect of perfluorination. Our study suggests that 3-fluorine-substitution in the pyridine moiety may be a useful means of antimutagenic structural modification in pyridine-fused aromatic chemicals for medicinal and agricultural use.
总共测试了12种喹啉（Q）的不同氟化衍生物在鼠伤寒沙门氏菌TA100中、存在S9混合物的情况下的致突变性，以研究低氟化喹啉的结构 - 致突变性关系。其中9种，即3,7 - 二氟、5,6 - 二氟、6,7 - 二氟、6,8 - 二氟、7,8 - 二氟、3,5,7 - 三氟、5,6,8 - 三氟、6,7,8 - 三氟和5,6,7,8 - 四氟喹啉（FQ），是为此新合成的。在3位氟化的那些均无致突变性。在5位或7位进行氟取代会增强致突变性，但在3 - FQ（即3,5 - 二氟、3,7 - 二氟和3,5,7 - 三氟喹啉）中则不然。一些6 - 氟化衍生物每剂量诱导回复突变体方面的最大诱导回复突变体较少，但致突变能力比喹啉更强。在8位进行氟取代未发生明显变化。这些结果表明，二氟和三氟取代对致突变性的影响通常是累加的，而四氟化的影响接近全氟化的钝化作用。我们的研究表明，吡啶部分的3 - 氟取代可能是对用于医药和农业的吡啶稠合芳香化学品进行抗诱变结构修饰的一种有用方法。
