Abstract
Fluoroquinolone (FQ) derivatives with environmental friendliness regarding photodegradation, bioconcentration, and genotoxicity were selected from our previous works so that their transformation pathways of biological metabolism, photodegradation, microbial degradation, and chlorination disinfection could be studied. The pathways of these molecules and their derivatives were simulated to investigate the genotoxicity of their transformation products. The results showed that the genotoxicity of the biological metabolites, photodegradation products, and microbial degradation products of the maternal FQ derivatives partially increased, whereas the disinfection by-products exhibited lower genotoxicity than their precursors. Some designed FQ molecular derivatives still had potential environmental risks in biological metabolism, photodegradation, and microbial degradation. This study demonstrated that it is necessary to take into account the potential environmental risks of the transformed products of the modified FQs molecules during biometabolism, photodegradation, microbial degradation, and chlorination processes when designing novel FQ molecules. In future studies, assessing the potential environmental risks during various artificial or natural processes can be applied to screen environmentally friendly novel FQ molecules to avoid and or reduce their threat to environmental and human health.
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Antoniocolabufo N, Perrone R, Berardi F, Perrone R, Colabufo NA (2016) Design and synthesis of new selective P-gp substrates and inhibitors. Curr Pharm Des 22(38):5774–5778. https://doi.org/10.2174/1381612822666160810114008
Balaban AT (1998) Topological and stereochemical molecular descriptors for databases useful in QSAR: similarity/dissimilarity and drug design. SAR QSAR Environ Res 8(1–2):1–21. https://doi.org/10.1080/10629369808033259
Chen RD, Wu BL (2006) Discussion on the mechanism of antibiotic resistance. Fujian J Anim Husb Vet Med 28(1):59–60
Chen YS, Zhang HB, Luo YM, Hu GJ, Zhao YG, Song J (2010) A preliminary study on the occurrence and dissipation of antibiotics in swine wastewater. Acta Sci Circumst 30(11):2205–2212. https://doi.org/10.13671/j.hjkxxb.2010.11.007
Chen Y, Cai X, Jiang L, Li Y (2016) Prediction of octanol-air partition coefficients for polychlorinated biphenyls (PCBs) using 3D-QSAR models. Ecotoxicol Environ Saf 124:202–212. https://doi.org/10.1016/j.ecoenv.2015.10.024
Chen H, Liu S, Xu XR, Diao ZH, Sun KF, Hao QW, Liu SS, Ying GG (2017) Tissue distribution, bioaccumulation characteristics and health risk of antibiotics in cultured fish from a typical aquaculture area. J Hazard Mater 343:140–148. https://doi.org/10.1016/j.jhazmat.2017.09.017
Di JB, Shi L, Wang G, Lang L (2017) Study on the biological activity and toxicity of environmental residual antibiotic degradation products. China Acad J Electron Publ House 4:4588–4593
Domagala JM (1994) Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J Antimicrob Chemother 33(4):685–706. https://doi.org/10.1093/jac/33.4.685
Dong QQ (2018) Photochemical transformation behavior of different dissociated species of fluoroquinolone and tetracycline antibiotics. Dalian Maritime University, Dalian
Fang Z, Ren HX, Xu X, Chen BH, Su R, Sun CH (2012) Analysis on the metabolites of enrofloxacin in the plasma of rabbit by HPLC-DAD-M Sn. Chin J Vet Drugs 46(2):19–22. https://doi.org/10.3969/j.issn.1002-1280.2012.02.008
Fraqueza MJ (2015) Antibiotic resistance of lactic acid bacteria isolated from dry-fermented sausages. Int J Food Microbiol 212:76–88. https://doi.org/10.1016/j.ijfoodmicro.2015.04.035
Ge LK (2009) Effects of aqueous dissolved matter on photodegradation of phenicol and fluoroquinolone antibiotics. Dalian University of Technology, Dalian. https://doi.org/10.7666/d.y1602269
Gootz TD (2001) Bactericidal assays for fluoroquinolones. Methods Mol Biol 95:185–194. https://doi.org/10.1385/1-59259-057-8:185
Guo J, Zhang YL, Zhou XF, Liu ZG (2016) Occurrence and removal of fluoroquinolones in municipal sewage. Environ Pollut Control 38(2):75–80
Huang JJ, Hu HY, Tang F, Li Y, Lu SQ, Lu Y (2011) Inactivation and reactivation of antibiotic-resistant bacteria by chlorination in secondary effluents of a municipal wastewater treatment plant. Water Res 45(9):2775–2781. https://doi.org/10.1016/j.watres.2011.02.026
Huang J, Xue YL, Xu H, Luo M (2017) Residual levels of fluoroquinolones in freshwater fish from aquatic products markets in Guiyang. J Environ Health 34(2):139–141. https://doi.org/10.16241/j.cnki.1001-5914.2017.02.011
Hurlbut JA, Gonzales SA, Storey JM, Roybal J, Walker CC, Pfenning AP, Turnipseed SB (2002) Concurrent determination of four fluoroquinolones in catfish, shrimp, and salmon by liquid chromatography with fluorescence detection. J AOAC Int 85(6):1293–1301. https://doi.org/10.1080/09637480220164370
Jia X (2009) Preliminary studies on metabolism and impact on main P450 isoenzymes of enrofloxacin in Carasius auratus gibelio liver microsome. Sichuan Agricultural University, Ya’an
Jiang W, Wang Z, Beier RC, Jiang H, Wu Y, Shen J (2013) Simultaneous determination of 13 fluoroquinolones and 22 sulfonamide residues in milk by a dual-colorimetric enzyme-linked immunosorbent assay. Anal Chem 85(4):1995–1999. https://doi.org/10.1021/ac303606h
Johnston L, Mackay L, Croft M (2002) Determination of quinolones and fluoroquinolones in fish tissue and seafood by high-performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection. J Chromatogr A 982(1):97–109. https://doi.org/10.1016/S0021-9673(02)01407-3
Jones OA, Lester JN, Voulvoulis N (2005) Pharmaceuticals: a threat to drinking water. Trends Biotechnol 23(4):163–167. https://doi.org/10.1016/j.tibtech.2005.02.001
Juhel-Gaugain M, Abjean JP (1998) Screening of quinolone residues in pig muscle by planar chromatography. Chromatographia 47(1–2):101–104. https://doi.org/10.1007/bf02466795
Karl W, Schneider J, Wetzstein HG (2006) Outlines of an “exploding” network of metabolites generated from the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum. Appl Microbiol Biotechnol 71(1):101–113. https://doi.org/10.1007/s00253-005-0177-5
Klaus K (2009) Antibiotics in the aquatic environment: a review—part I. Chemosphere 75(4):417–434. https://doi.org/10.1016/j.chemosphere.2008.11.086
Leung HW, Minh TB, Murphy MB, Lam James CW, So MK, Martin M, Lam Paul KS, Richardson BJ (2012) Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China. Environ Int 42:1–9. https://doi.org/10.1016/j.envint.2011.03.004
Li M (2014) Toxicity variation of quinolone antibiotics in chlorination system. University of Chinese Academy of Sciences, Beijing
Li Y, Niu J, Wang W (2011) Photolysis of Enrofloxacin in aqueous systems under simulated sunlight irradiation: kinetics, mechanism and toxicity of photolysis products. Chemosphere 85(5):892–897. https://doi.org/10.1016/j.chemosphere.2011.07.008
Li M, Wei DB, Zhao HM, Du YG (2013) Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation Using 2D and 3D models. Chemosphere 95:220–226. https://doi.org/10.1016/j.chemosphere.2013.09.002
Liu F, Ying GG, Tao R, Zhao JL, Yang JF, Zhao LF (2009a) Effects of six selected antibiotics on plant growth and soil microbial and enzymatic activities. Environ Pollut 157(5):1636–1642. https://doi.org/10.1016/j.envpol.2008.12.021
Liu W, Wang H, Chen XJ, Yang DW, Kuang GW, Sun ZL (2009b) Progress on degradation of antibiotics in environment. Progr Vet Med 30(3):89–94
Liu YW, Li ZJ, Feng Y, Cheng DM, Hu HY, Zhang WJ (2016) Research progress of microbial degradation of antibiotics. J Agro-Environ Sci 35(2):212–224. https://doi.org/10.11654/jaes.2016.02.002
Liu S, Zhao H, Lehmler HJ, Cai X, Chen J (2017) Antibiotic pollution in marine food webs in Laizhou bay, North China: trophodynamics and human exposure implication. Environ Sci Technol 51(4):2392–2400. https://doi.org/10.1021/acs.est.6b04556
Meng L, Yang B, Xue N (2015) A review on environmental behaviors and ecotoxicology of fluoroquinolone antibiotics. Asian J Ecotoxicol 10(2):76–88. https://doi.org/10.7524/AJE.1673-5897.20141118006
Morales-Gutiérrez FJ, Barbosa J, Barrón D (2015) Metabolic study of enrofloxacin and metabolic profile modifications in broiler chicken tissues after drug administration. Food Chem 172:30–39. https://doi.org/10.1016/j.foodchem.2014.09.025
Nagayma T, Sasamoto T, Takeba K, Nakajima T, Matushima Y et al (2010) Rapid determination of fluoroquinolone residues in honey by a microbiological screening method and liquid chromatography. J AOAC Int 93(4):1331–1339
Qu R, Liu H, Feng M, Yang X, Wang Z (2012) Investigation on intramolecular hydrogen bond and some thermodynamic properties of polyhydroxylated anthraquinones. J Chem Eng Data 57:2442–2455. https://doi.org/10.1021/je300407g
Richardson BJ, Lame PKS, Martin M (2005) Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China. Mar Pollut Bull 50(9):913–920. https://doi.org/10.1016/j.marpolbul.2005.06.034
Schlüsener MP, Bester K (2006) Persistence of antibiotics such as macrolides, tiamulin and salinomycin in soil. Environ Pollut 143(3):565–571. https://doi.org/10.1016/j.envpol.2005.10.049
Ståle J, Frost TK (2011) Application of quantitative risk assessment in produced water management: the environmental impact factor (EIF). In: Lee K, Neff J (eds) produced water. Springer, New York. https://doi.org/10.1007/978-1-4614-0046-2-27
Su W, Wang SW, Jin XF, Mu YC (2014) Study on residue distribution of three kinds of fluoroquinolones in different tissues of Sansui duck. J Mt Agric Biol 33(6):051–054. https://doi.org/10.1080/13632752.2012.704318
Tian Y, Zhang ZJ, Li J, Li WJ, Chen Y (2010) Multiresidue determination of fluoroquinolones in eggs by solid-phase extraction-LC–MS/MS. J China Pharm Univ 41(1):60–65
Tittlemier SA, Gélinas JM, Dufresne G, Haria M, Querry J, Cleroux C, Ménard C, Delahaut P, Singh G, Fischer-Durand N, Godefroy SB (2008) Development of a direct competitive enzyme-linked immunosorbent assay for the detection of fluoroquinolone residues in shrimp. Food Anal Methods 1(1):28–35. https://doi.org/10.1007/s12161-007-9004-1
Van Doorslaer X, Dewulf J, Van Langenhove H, Demeestere K (2014) Fluoroquinolone antibiotics: an emerging class of environmental micropollutants. Sci Total Environ 500–501(1–3):250–269. https://doi.org/10.1016/j.scitotenv.2014.08.075
Vega VA, Schenck FJ, Mcmullen SE (2009) Rapid method for the determination and confirmation of fluoroquinolone residues in catfish using liquid chromatography/fluorescence detection and liquid chromatography-tandem mass spectrometry. J AOAC Int 92(4):1233–1240. https://doi.org/10.1111/j.1365-2621.2009.01979.x
Vilar S, Cozza GS (2008) Medicinal chemistry and the molecular operating environment (MOE): application of QSAR and molecular docking to drug discovery. Curr Top Med Chem 8(18):1555–1572. https://doi.org/10.2174/156802608786786624
Wang N, Noemie N, Hien NN, Huynh TT, Frederic S, Phuong NT, Sophie D, Joëlle W, Caroline D, Scippo ML, Patrick K, Huong DTT (2009) Adverse effects of enrofloxacin when associated with environmental stress in Tra catfish (Pangasianodon hypophthalmus). Chemosphere 77(11):1577–1584. https://doi.org/10.1016/j.chemosphere.2009.09.038
Wang XL, Gu WW, Guo EM, Cun CY, Li Y (2017) Assessment of long-range transport potential of polychlorinated naphthalenes based on three-dimensional QSAR models. Environ Sci Pollut Res 24(17):14802–14818. https://doi.org/10.1007/s11356-017-8967-8
Wetzstein HG, Schmeer N, Karl W (1998) Degradation of the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum: identification of metabolites. Appl Environ Microbiol 64(3):4272–4281. https://doi.org/10.1002/pad.467
Winkler DA (2018) Sparse QSAR modelling methods for therapeutic and regenerative medicine. J Comput Aided Mol Des 32(2):1–13. https://doi.org/10.1007/s10822-018-0106-1
Witte BD, Langenhove HV, Hemelsoet K (2009) Levofloxacin ozonation in water: rate determining process parameters and reaction pathway elucidation. Chemosphere 76(5):683–689. https://doi.org/10.1016/j.chemosphere.2009.03.048
Wu YR, Lu Y, Wu Y (2009) Determination of fluoroquinolone residues in beef by high performance liquid chromatography-electrospray ionization mass spectrometry. Food Sci 30(20):387–390. https://doi.org/10.1007/978-3-540-85168-4-52
Xu W, Zhang G, Li X, Zou SC, Li P, Hu ZH, Li J (2007) Occurrence and elimination of antibiotics at four sewage treatment plants in the Pearl River Delta (PRD), South China. Water Res 41(19):4526–4534. https://doi.org/10.1016/j.watres.2007.06.023
Xu WH, Zhang G, Zou SC, Ling ZH, Wang GL, Yan W (2009) A preliminary investigation on the occurrence and distribution of antibiotics in the yellow river and its tributaries, China. Water Environ Res 81(3):248–254. https://doi.org/10.2175/106143008X325719
Yin JX (2012) Transformation mechanism and toxicity assessment of levofloxacin in oxidation process. Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing. http://www.doc88.com/p-7059829776517.html. Accessed 2 Oct 2018
Zhang W (1999) HPLC simple analysis method for quinolone residues in meat. Foreign Med Sci Sect Hyg 6:384
Zhao XH, Chu ZH, Li Y (2018a) Molecular design of lower photodegradation fluoroquinolone antibiotics and their photolysis paths inference. Chem J Chin Univ 39(12):2707–2718. https://doi.org/10.7503/cjcu20180475
Zhao HX, Chen M, Quan WN, Liu WY, Chen JW (2018b) Analysis on the metabolites of enrofloxacin in aquatic organism. Environ Sci Technol 41(10):157–161. https://doi.org/10.19672/j.cnki.1003-6504.2018.10.02
Zhao XH, Zhao YY, Ren ZX, Li Y (2019a) Combined QSAR/QSPR and molecular docking study on fluoroquinolones to reduce biological enrichment. Comput Biol Chem 79:177–184. https://doi.org/10.1016/j.compbiolchem.2019.02.008
Zhao XH, Wang XL, Li Y (2019b) Combined HQSAR method and molecular docking study on genotoxicity mechanism of quinolones with higher genotoxicity. Environ Sci Pollut Res. https://doi.org/10.1007/s11356-019-06482-3
Zhou XF, Dai CM, Zhang YL, Shi L (2008) Pollution status of fluoroquinolones in water environment and their analysis methods. Environ Prot Chem Ind 28(6):505–508
Zou S, Xu W, Zhang R, Tang JH, Chen YJ, Zhang G (2011) Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: impacts of river discharge and aquaculture activities. Environ Pollut 159(10):2913–2920. https://doi.org/10.1016/j.envpol.2011.04.037
Acknowledgements
The authors thank American Journal Experts (http://www.aje.cn/ac) for editing the English text of a draft of this manuscript.
Funding
This work was supported by the Key Projects in the National Science & Technology Pillar Program in the Eleventh Five-Year Plan Period [No. 2008BAC43B01].
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Zhang, W., Sun, R., Zhao, X. et al. Environmental Conversion Path Inference of New Designed Fluoroquinolones and Their Potential Environmental Risk. Arch Environ Contam Toxicol 78, 310–328 (2020). https://doi.org/10.1007/s00244-019-00672-3
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DOI: https://doi.org/10.1007/s00244-019-00672-3