Clastogenicity of Quinoline and Monofluorinated Quinolines in Chinese Hamster Lung Cells

Suzuki, Takayoshi; Takeshita, Kenji; Saeki, Ken-ichi; Kadoi, Minoru; Hayashi, Makoto; Sofuni, Toshio

doi:10.1248/jhs.53.325

Cited by 11 publications

(4 citation statements)

References 19 publications

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“…According to Uno et al [ 60 ], quinoline derivatives does not induce the formation of micronucleus events in the bone marrow and gastrointestinal tract cells of rats. Similarly, for Suzuki et al [ 61 ], structural modifications in a quinoline derivative were unable to induce the formation of micronucleated lung fibroblast cells in the hamster. In opposition to these findings, antifungals used against candidiasis and dermatophytosis can induce severe mutagenicity in the cells of the patient.…”

Section: Resultsmentioning

confidence: 73%

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis

et al. 2020

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Fungal infections have emerged as a current serious global public health problem. The main problem involving these infections is the expansion of multidrug resistance. Therefore, the prospection of new compounds with efficacy antifungal becomes necessary. Thus, this study evaluated the antifungal profile and toxicological parameters of quinolines derivatives against Candida spp. and dermatophyte strains. As a result, a selective anti-dermatophytic action was demonstrated by compound 5 (geometric means (GM = 19.14 μg ml −1 )). However, compounds 2 (GM = 50 μg ml −1 ) and 3 (GM = 47.19 μg ml −1 ) have presented only anti- Candida action. Compounds 3 and 5 did not present cytotoxic action. Compound 5 did not produce dermal and mucosal toxicity. In addition, this compound showed the absence of genotoxic potential, suggesting safety for topical and systemic use. Quinolines demonstrated a potent anti-dermatophytic and anti-yeast action. Moreover, compound 5 presented an excellent toxicological profile, acting as a strong candidate for the development of a new effective and safe compound against dermatophytosis of difficult treatment. Electronic supplementary material The online version of this article (10.1007/s42770-020-00348-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 73%

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis

et al. 2020

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“…The same effects for the 6-methylated and the parent quinoline were found by Debnath et al [37] . The latter substance was also shown to cause significant induction of liver micronuclei and chromosome aberrations in rats and the hamster lung fibroblast cell line CHL/IU [11] , [38] , [39] , [40] and is a potent hepatocarcinogen in mice and rats [41] , [42] , [43] . Indole was positive in the Ames assay [44] .…”

Section: Resultsmentioning

confidence: 99%

Genotoxicity of Heterocyclic PAHs in the Micronucleus Assay with the Fish Liver Cell Line RTL-W1

et al. 2014

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Heterocyclic aromatic hydrocarbons are, together with their un-substituted analogues, widely distributed throughout all environmental compartments. While fate and effects of homocyclic PAHs are well-understood, there are still data gaps concerning the ecotoxicology of heterocyclic PAHs: Only few publications are available investigating these substances using in vitro bioassays. Here, we present a study focusing on the identification and quantification of clastogenic and aneugenic effects in the micronucleus assay with the fish liver cell line RTL-W1 that was originally derived from rainbow trout (Oncorhynchus mykiss). Real concentrations of the test items after incubation without cells were determined to assess chemical losses due to, e.g., sorption or volatilization, by means of gas chromatography-mass spectrometry. We were able to show genotoxic effects for six compounds that have not been reported in vertebrate systems before. Out of the tested substances, 2,3-dimethylbenzofuran, benzothiophene, quinoline and 6-methylquinoline did not cause substantial induction of micronuclei in the cell line. Acridine caused the highest absolute induction. Carbazole, acridine and dibenzothiophene were the most potent substances compared with 4-nitroquinoline oxide, a well characterized genotoxicant with high potency used as standard. Dibenzofuran was positive in our investigation and tested negative before in a mammalian system. Chemical losses during incubation ranged from 29.3% (acridine) to 91.7% (benzofuran) and may be a confounding factor in studies without chemical analyses, leading to an underestimation of the real potency. The relative potency of the investigated substances was high compared with their un-substituted PAH analogues, only the latter being typically monitored as priority or indicator pollutants. Hetero-PAHs are widely distributed in the environment and even more mobile, e.g. in ground water, than homocyclic PAHs due to the higher water solubility. We conclude that this substance class poses a high risk to water quality and should be included in international monitoring programs.

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“…Different studies on the structure–genotoxicity relationship of Qs have shown that the incorporation of certain substituents in the Q core change their clastogenicity, mutagenicity, and carcinogenicity. For example, as indicated in Figure , a fluorine moiety incorporated at positions C‐5 and C‐7 of Q increases significantly its genotoxic activity; however, the incorporation at position C‐3 produces a complete reduction of its genotoxicity in different experimental models (LaVoie et al, ; Saeki et al, ,b; Miyata et al, ; Kato et al, ; Hakura et al, ; Suzuki et al, ). It has been also demonstrated that chlorine and fluorine incorporation at positions C‐2 and C‐3 of Q, respectively, result in the reduction of its carcinogenicity (Hirao et al, ; Saeki et al, ).…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

Duran

Rincón

Galvis

et al. 2013

Environmental Toxicology

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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.

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Clastogenicity of Quinoline and Monofluorinated Quinolines in Chinese Hamster Lung Cells

Cited by 11 publications

References 19 publications

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis

Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis

Genotoxicity of Heterocyclic PAHs in the Micronucleus Assay with the Fish Liver Cell Line RTL-W1

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest

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