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Chemosphere. 2014 Jan;95:220-6. doi: 10.1016/j.chemosphere.2013.09.002. Epub 2013 Sep 27.

Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation using 2D and 3D models.

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  • 1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address: bkdlimin@126.com.

Abstract

The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay. Some quinolones exhibited high genotoxicity, and the chemical substituent on quinolone ring significantly affected genotoxicity. To establish the relationship between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical parameters was developed. Calculation suggested that both steric and electrostatic properties were correlated well with genotoxicity. Furthermore, the specific effect on three key active sites (1-, 7- and 8-positions) of quinolone ring was investigated using a 3D-QSAR (comparative molecular field analysis, CoMFA) method. From our modeling, the genotoxicity increased when substituents had: (1) big volume and/or positive charge at 1-position; (2) negative charge at 7-position; and (3) small volume and/or negative charge at 8-position. The developed QSAR models were applicable to estimate genotoxicity of quinolones antibiotics and their transformation products. It is noted that some of the transformation products exhibited higher genotoxicity comparing to their precursor (e.g., ciprofloxacin). This study provided an alternative way to understand the molecule genotoxicity of quinolones derivatives, as well as to evaluate their potential environmental risks.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

CoMFA; Genotoxicity; QSAR; Quinolone

PMID:
24080009
[PubMed - indexed for MEDLINE]
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