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Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs

Most studies on adverse drug reactions (ADRs) of fluoroquinolones (FQs) have focused on the mechanisms of single ADRs, and no quantitative structure–activity relationship (QSAR) method studies have been carried out that combine several ADRs of FQs. In this study, an improved three-dimensional (3D) Q...

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Autores principales: Ren, Zhixing, Wang, Yingwei, Xu, Haihong, Li, Yufei, Han, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747076/
https://www.ncbi.nlm.nih.gov/pubmed/31470687
http://dx.doi.org/10.3390/ijerph16173161
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author Ren, Zhixing
Wang, Yingwei
Xu, Haihong
Li, Yufei
Han, Song
author_facet Ren, Zhixing
Wang, Yingwei
Xu, Haihong
Li, Yufei
Han, Song
author_sort Ren, Zhixing
collection PubMed
description Most studies on adverse drug reactions (ADRs) of fluoroquinolones (FQs) have focused on the mechanisms of single ADRs, and no quantitative structure–activity relationship (QSAR) method studies have been carried out that combine several ADRs of FQs. In this study, an improved three-dimensional (3D) QSAR method was established using fuzzy comprehensive evaluation. This method could simultaneously consider three common ADRs of FQs using molecular parameters. The improved method could comprehensively predict three ADRs of FQs and provide direction for the development of new drugs with lower ADRs than the originals. According to the improved method, 48 derivatives with lower ADRs (decreased by 4.86% to 50.92%) were designed from pazufloxacin. Three derivatives with a higher genotoxicity, higher photodegradation, and lower bioconcentration than pazufloxacin were selected using the constructed QSAR methods of the FQs. Finally, three traditional 3D-QSAR methods of single ADR were constructed to validate the improved method. The improved method was reasonable, with a relative error range of 0.96% to 4.30%. This study provides valuable reference data and will be useful for the development of strategies to produce new drugs with few ADRs. In the absence of complementary biological studies of these adverse drug reactions, the results reported here may be quite divergent from those found in humans or experimental animals in vivo. One major reason for this is that many adverse drug reactions are dependent upon enzyme-catalyzed metabolic activation (toxication) or on non-enzymatic conversion to toxic products and are not due to the parent drug moiety.
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spelling pubmed-67470762019-09-27 Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs Ren, Zhixing Wang, Yingwei Xu, Haihong Li, Yufei Han, Song Int J Environ Res Public Health Article Most studies on adverse drug reactions (ADRs) of fluoroquinolones (FQs) have focused on the mechanisms of single ADRs, and no quantitative structure–activity relationship (QSAR) method studies have been carried out that combine several ADRs of FQs. In this study, an improved three-dimensional (3D) QSAR method was established using fuzzy comprehensive evaluation. This method could simultaneously consider three common ADRs of FQs using molecular parameters. The improved method could comprehensively predict three ADRs of FQs and provide direction for the development of new drugs with lower ADRs than the originals. According to the improved method, 48 derivatives with lower ADRs (decreased by 4.86% to 50.92%) were designed from pazufloxacin. Three derivatives with a higher genotoxicity, higher photodegradation, and lower bioconcentration than pazufloxacin were selected using the constructed QSAR methods of the FQs. Finally, three traditional 3D-QSAR methods of single ADR were constructed to validate the improved method. The improved method was reasonable, with a relative error range of 0.96% to 4.30%. This study provides valuable reference data and will be useful for the development of strategies to produce new drugs with few ADRs. In the absence of complementary biological studies of these adverse drug reactions, the results reported here may be quite divergent from those found in humans or experimental animals in vivo. One major reason for this is that many adverse drug reactions are dependent upon enzyme-catalyzed metabolic activation (toxication) or on non-enzymatic conversion to toxic products and are not due to the parent drug moiety. MDPI 2019-08-29 2019-09 /pmc/articles/PMC6747076/ /pubmed/31470687 http://dx.doi.org/10.3390/ijerph16173161 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ren, Zhixing
Wang, Yingwei
Xu, Haihong
Li, Yufei
Han, Song
Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title_full Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title_fullStr Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title_full_unstemmed Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title_short Fuzzy Comprehensive Evaluation Assistant 3D-QSAR of Environmentally Friendly FQs to Reduce ADRs
title_sort fuzzy comprehensive evaluation assistant 3d-qsar of environmentally friendly fqs to reduce adrs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747076/
https://www.ncbi.nlm.nih.gov/pubmed/31470687
http://dx.doi.org/10.3390/ijerph16173161
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