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Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest
Author(s) -
Díaz Duran Leidy Tatiana,
Olivar Rincón Nathalia,
Puerto Galvis Carlos Eduardo,
Kouznetsov Vladimir V.,
Fuentes Lorenzo Jorge Luis
Publication year - 2015
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.21905
Subject(s) - genotoxicity , quinoline , chemistry , ames test , stereochemistry , epoxide , nitro , substituent , medicinal chemistry , combinatorial chemistry , organic chemistry , toxicity , alkyl , bacteria , biology , salmonella , genetics , catalysis
Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4‐methylquinoline, 4‐nitroquinoline‐1‐oxide (4‐NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4‐methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C‐5 to C‐8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C‐2: phenyl and 3,4‐methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C‐2 substitution with α‐, β‐, or γ‐pyridinyl groups removed 4‐methylquinoline genotoxicity. On the other hand, 4‐NQO derivatives whose genotoxic mechanism involves reduction of the C‐4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C‐2 of 4‐NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure–genotoxicity relationships and bioassay‐guided quinoline synthesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 278–292, 2015.