An adjusted 3D-QSAR model for the combined activity of fluoroquinolones photodegradation and microbial degradation assisted by dynamic simulation and its application in molecular modification

Zhang, Wenhui; Gu, Wenwen; Sun, Ruihao; Zhou, Mengying; Han, Zhenzhen; Yu, Li

doi:10.1016/j.ecoenv.2021.111973

Cited by 17 publications

(2 citation statements)

References 45 publications

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“…Then, the leave-one-out (LOO) method and non-cross-validation regression (No Validation) method were respectively used for cross-validation analysis of the training set. The cross-validation coefficient Q 2 , the optimal principal component number N, the non-cross-validation coefficient R 2 , standard error of estimate (SEE) and test value F of the model were obtained [ 57 ]. In general, when the cross-validation coefficient Q 2 > 0.5 and the non-cross validation coefficient R 2 > 0.9 and close to 1, this indicated that the model has reliable prediction ability [ 58 ].…”

Section: Methodsmentioning

confidence: 99%

Potential Toxicity Risk Assessment and Priority Control Strategy for PAHs Metabolism and Transformation Behaviors in the Environment

Zhao

Zhou

Zhao

et al. 2022

IJERPH

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In this study, 16 PAHs were selected as the priority control pollutants to summarize their environmental metabolism and transformation processes, including photolysis, plant degradation, bacterial degradation, fungal degradation, microalgae degradation, and human metabolic transformation. Meanwhile, a total of 473 PAHs by-products generated during their transformation and degradation in different environmental media were considered. Then, a comprehensive system was established for evaluating the PAHs by-products’ neurotoxicity, immunotoxicity, phytotoxicity, developmental toxicity, genotoxicity, carcinogenicity, and endocrine-disrupting effect through molecular docking, molecular dynamics simulation, 3D-QSAR model, TOPKAT method, and VEGA platform. Finally, the potential environmental risk (phytotoxicity) and human health risks (neurotoxicity, immunotoxicity, genotoxicity, carcinogenicity, developmental toxicity, and endocrine-disrupting toxicity) during PAHs metabolism and transformation were comprehensively evaluated. Among the 473 PAH’s metabolized and transformed products, all PAHs by-products excluding ACY, CHR, and DahA had higher neurotoxicity, 152 PAHs by-products had higher immunotoxicity, and 222 PAHs by-products had higher phytotoxicity than their precursors during biological metabolism and environmental transformation. Based on the TOPKAT model, 152 PAH by-products possessed potential developmental toxicity, and 138 PAH by-products had higher genotoxicity than their precursors. VEGA predicted that 247 kinds of PAH derivatives had carcinogenic activity, and only the natural transformation products of ACY did not have carcinogenicity. In addition to ACY, 15 PAHs produced 123 endocrine-disrupting substances during metabolism and transformation. Finally, the potential environmental and human health risks of PAHs metabolism and transformation products were evaluated using metabolic and transformation pathway probability and degree of toxic risk as indicators. Accordingly, the priority control strategy for PAHs was constructed based on the risk entropy method by screening the priority control pathways. This paper assesses the potential human health and environmental risks of PAHs in different environmental media with the help of models and toxicological modules for the toxicity prediction of PAHs by-products, and thus designs a risk priority control evaluation system for PAHs.

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Section: Methodsmentioning

confidence: 99%

Potential Toxicity Risk Assessment and Priority Control Strategy for PAHs Metabolism and Transformation Behaviors in the Environment

Zhao

Zhou

Zhao

et al. 2022

IJERPH

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“…Li et al used density functional theory (DFT) to determine the molecular structure stability characterized by the positive frequency values [105]. Zhang et al reported using molecular metabolic stability and genotoxicity as indices for the functional evaluation of FQs derivatives [106]. Both Zhang et al and Hou et al reported using the HQSAR model for the genotoxicity of quinolones toward Salmonella typhimurium for predicting the negative logarithm lowest observed effect concentration (pLOEC) values, which were then used for characterizing bacterial genotoxicity [59,107].…”

Section: Evaluation Of the Functional Properties Of Nor Derivativesmentioning

confidence: 99%

Strategies to Control Human Health Risks Arising from Antibiotics in the Environment: Molecular Modification of QNs for Enhanced Plant–Microbial Synergistic Degradation

Sun

Zhao

2021

IJERPH

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In the present work, a comprehensive screening and evaluation system was established to improve the plant–microbial synergistic degradation effects of QNs. The study included the construction of a 3D-QSAR model, the molecular modification, environmental friendliness and functional evaluation of drugs, degradation pathway simulation, and human health risk assessment. Molecular dynamics was applied to quantify the binding capacity of QNs toward the plant degradation enzyme (peroxidase) and microbial degradation enzymes (manganese peroxidase, lignin peroxidase, and laccase). The fuzzy comprehensive evaluation method was used in combination with the weighted average method for normalization and assigning equal weights to the plant and microbial degradation effect values of the QNs. Considering the synergistic degradation effect value as the dependent variable and the molecular information of the QNs as the independent variable, a 3D-QSAR model was constructed for the plant–microbial synergistic degradation effect of QNs. The constructed model was then employed to conduct the molecular modification, environmental friendliness and functional evaluation, degradation pathway simulation, and human health risk assessment of transformation products using pharmacokinetics and toxicokinetics. The results revealed that the synergistic degradation effect 3D-QSAR (CoMSIA) model exhibited good internal and external prediction ability, fitting ability, stability, and no overfitting phenomenon. Norfloxacin (NOR) was used as the target molecule in the molecular modification. A total of 35 NOR derivatives with enhanced plant–microbial synergistic degradation effect (1.32–21.51%) were designed by introducing small-volume, strongly electronegative, and hydrophobic hydrogen bond receptor groups into the active group of the norfloxacin structure. The environment-friendliness and the functionality of NOR were evaluated prior to and after the modification, which revealed seven environment-friendly FQs derivatives exhibiting moderate improvement in stability and bactericidal efficacy. The simulation of the NOR plant and microbial degradation pathways prior to and after the modification and the calculation of the reaction energy barrier revealed Pathway A (D-17 to D-17-2) and Pathway B (D-17 to D-17-4) as the most prone degradation pathways in plants and Pathway A (D-17 to D-17-1) and Pathway B (D-17 to D-17-4) as the most prone degradation pathways in microorganisms. This demonstrated that the degradation of the modified NOR derivatives was significantly enhanced, with the hydroxylation and piperazine ring substitution reaction playing an important role in the degradation process. Finally, the parameters, including hepatotoxicity, mutagenicity, and rodent carcinogenicity, among others, predicted using the pharmacokinetics and toxicokinetics analyses revealed a significant reduction in the human health risk associated with the modified NOR, along with a considerable reduction in the toxicity of its transformation products, implying that the human health risk associated with the transformation products was reduced remarkably. The present study provides a theoretical basis for novel ideas and evaluation programs for improving the plant–microbial synergistic degradation of the QNs antibiotics for source control and drug design, thereby reducing the residues of these antibiotics and the associated hazard in the complex plant–soil environment, ultimately decreasing the potential risks to human health.

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Promotional effect of Ca doping on Bi2Fe4O9 as peroxymonosulfate activator for gatifloxacin removal

et al. 2022

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An adjusted 3D-QSAR model for the combined activity of fluoroquinolones photodegradation and microbial degradation assisted by dynamic simulation and its application in molecular modification

Cited by 17 publications

References 45 publications

Potential Toxicity Risk Assessment and Priority Control Strategy for PAHs Metabolism and Transformation Behaviors in the Environment

Potential Toxicity Risk Assessment and Priority Control Strategy for PAHs Metabolism and Transformation Behaviors in the Environment

Strategies to Control Human Health Risks Arising from Antibiotics in the Environment: Molecular Modification of QNs for Enhanced Plant–Microbial Synergistic Degradation

Promotional effect of Ca doping on Bi2Fe4O9 as peroxymonosulfate activator for gatifloxacin removal

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