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

Meijin Du, Dan Zhang, Yilin Hou, Xiaohui Zhao and Yu Li
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Meijin Du: College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China
Dan Zhang: Jilin Province Shize Environmental Protection Technology Co., Ltd, Jilin 130012, China
Yilin Hou: College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China
Xiaohui Zhao: College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China
Yu Li: College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China

IJERPH, 2019, vol. 16, issue 21, 1-14

Abstract: 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.

Keywords: fluoroquinolone molecules; genotoxicity; 2D-QSAR model; principal component analysis; sensitivity analysis; molecular design (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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