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Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity

In this paper, two-dimensional quantitative structure–activity relationship (2D-QSAR) and principal component analysis (PCA) methods were employed to screen the main parameters affecting the genotoxicity of fluoroquinolones (FQs), and the rules affecting the genetic toxicity of FQs were investigated...

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Autores principales: Du, Meijin, Zhang, Dan, Hou, Yilin, Zhao, Xiaohui, Li, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862474/
https://www.ncbi.nlm.nih.gov/pubmed/31661905
http://dx.doi.org/10.3390/ijerph16214156
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author Du, Meijin
Zhang, Dan
Hou, Yilin
Zhao, Xiaohui
Li, Yu
author_facet Du, Meijin
Zhang, Dan
Hou, Yilin
Zhao, Xiaohui
Li, Yu
author_sort Du, Meijin
collection PubMed
description In this paper, two-dimensional quantitative structure–activity relationship (2D-QSAR) and principal component analysis (PCA) methods were employed to screen the main parameters affecting the genotoxicity of fluoroquinolones (FQs), and the rules affecting the genetic toxicity of FQs were investigated by combining 2D-QSAR and PCA with the sensitivity analysis method. First, four types of parameters were calculated, namely, the geometric parameters (7), electronic parameters (5), physical and chemical parameters (8), and spectral parameters (7), but the physical and chemical parameters heat of formation (HF) and critical volume (CV) were excluded after the establishment of the 2D-QSAR model. Then, after PCA, it was found that the first principal component represented the main driving factors affecting the molecular genetic toxicity of FQs. In addition, after comprehensive analysis of the factor loading of the first, second, and third principal components, seven parameters affecting the genotoxicity of the FQs were screened out, namely, total energy (TE), critical temperature (CT), and molecular weight (Mol Wt) (increased with increasing genotoxicity of the FQs) and steric parameter (MR), quadrupole moment Q(XX) (Q(XX)), quadrupole moment Q(YY) (Q(YY)), and boiling point (BP) (decreased with increasing genotoxicity of the FQs); the above key parameters were also verified by sensitivity analysis. The obtained rules could be used to determine the substitution sites and the substitution groups associated with higher genotoxicity in the process of FQ modification, and these rules agreed well with the hologram quantitative structure–activity relationship (HQSAR) model. Finally, it was also found through SPSS analysis that the parameters screened in this paper were significantly correlated with FQ derivatives’ genetic toxicity.
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spelling pubmed-68624742019-12-05 Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity Du, Meijin Zhang, Dan Hou, Yilin Zhao, Xiaohui Li, Yu Int J Environ Res Public Health Article In this paper, two-dimensional quantitative structure–activity relationship (2D-QSAR) and principal component analysis (PCA) methods were employed to screen the main parameters affecting the genotoxicity of fluoroquinolones (FQs), and the rules affecting the genetic toxicity of FQs were investigated by combining 2D-QSAR and PCA with the sensitivity analysis method. First, four types of parameters were calculated, namely, the geometric parameters (7), electronic parameters (5), physical and chemical parameters (8), and spectral parameters (7), but the physical and chemical parameters heat of formation (HF) and critical volume (CV) were excluded after the establishment of the 2D-QSAR model. Then, after PCA, it was found that the first principal component represented the main driving factors affecting the molecular genetic toxicity of FQs. In addition, after comprehensive analysis of the factor loading of the first, second, and third principal components, seven parameters affecting the genotoxicity of the FQs were screened out, namely, total energy (TE), critical temperature (CT), and molecular weight (Mol Wt) (increased with increasing genotoxicity of the FQs) and steric parameter (MR), quadrupole moment Q(XX) (Q(XX)), quadrupole moment Q(YY) (Q(YY)), and boiling point (BP) (decreased with increasing genotoxicity of the FQs); the above key parameters were also verified by sensitivity analysis. The obtained rules could be used to determine the substitution sites and the substitution groups associated with higher genotoxicity in the process of FQ modification, and these rules agreed well with the hologram quantitative structure–activity relationship (HQSAR) model. Finally, it was also found through SPSS analysis that the parameters screened in this paper were significantly correlated with FQ derivatives’ genetic toxicity. MDPI 2019-10-28 2019-11 /pmc/articles/PMC6862474/ /pubmed/31661905 http://dx.doi.org/10.3390/ijerph16214156 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
Du, Meijin
Zhang, Dan
Hou, Yilin
Zhao, Xiaohui
Li, Yu
Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title_full Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title_fullStr Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title_full_unstemmed Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title_short Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
title_sort combined 2d-qsar, principal component analysis and sensitivity analysis studies on fluoroquinolones’ genotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862474/
https://www.ncbi.nlm.nih.gov/pubmed/31661905
http://dx.doi.org/10.3390/ijerph16214156
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