IDEAS home Printed from https://ideas.repec.org/a/gam/jijerp/v18y2021i20p10610-d653108.html
   My bibliography  Save this article

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

Author

Listed:
  • Peixuan Sun

    (College of New Energy and Environment, Jilin University, Changchun 130012, China)

  • Wenjin Zhao

    (College of New Energy and Environment, Jilin University, Changchun 130012, China)

Abstract

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.

Suggested Citation

  • Peixuan Sun & Wenjin Zhao, 2021. "Strategies to Control Human Health Risks Arising from Antibiotics in the Environment: Molecular Modification of QNs for Enhanced Plant–Microbial Synergistic Degradation," IJERPH, MDPI, vol. 18(20), pages 1-26, October.
  • Handle: RePEc:gam:jijerp:v:18:y:2021:i:20:p:10610-:d:653108
    as

    Download full text from publisher

    File URL: https://www.mdpi.com/1660-4601/18/20/10610/pdf
    Download Restriction: no

    File URL: https://www.mdpi.com/1660-4601/18/20/10610/
    Download Restriction: no
    ---><---

    References listed on IDEAS

    as
    1. Lu-ze Yang & Miao Liu, 2020. "A Double-Activity (Green Algae Toxicity and Bacterial Genotoxicity) 3D-QSAR Model Based on the Comprehensive Index Method and Its Application in Fluoroquinolones’ Modification," IJERPH, MDPI, vol. 17(3), pages 1-14, February.
    2. Xixi Li & Baiyu Zhang & Wendy Huang & Cuirin Cantwell & Bing Chen, 2020. "Integration of Fuzzy Matter-Element Method and 3D-QSAR Model for Generation of Environmentally Friendly Quinolone Derivatives," IJERPH, MDPI, vol. 17(9), pages 1-25, May.
    3. Yilin Hou & Yuanyuan Zhao & Yu Li, 2020. "Environmentally Friendly Fluoroquinolone Derivatives with Lower Plasma Protein Binding Rate Designed Using 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation," IJERPH, MDPI, vol. 17(18), pages 1-18, September.
    4. Andrzej M. Brzozowski & Ashley C. W. Pike & Zbigniew Dauter & Roderick E. Hubbard & Tomas Bonn & Owe Engström & Lars Öhman & Geoffrey L. Greene & Jan-Åke Gustafsson & Mats Carlquist, 1997. "Molecular basis of agonism and antagonism in the oestrogen receptor," Nature, Nature, vol. 389(6652), pages 753-758, October.
    5. Si-cheng Liu & Shi-jun Sun & Peng Cui & Yi-fan Ding, 2019. "Molecular Modification of Fluoroquinolone-Biodegrading Enzymes Based on Molecular Docking and Homology Modelling," IJERPH, MDPI, vol. 16(18), pages 1-33, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Peixuan Sun & Yuanyuan Zhao & Luze Yang & Zhixing Ren & Wenjin Zhao, 2020. "Environmentally Friendly Quinolones Design for a Two-Way Choice between Biotoxicity and Genotoxicity through Double-Activity 3D-QSAR Model Coupled with the Variation Weighting Method," IJERPH, MDPI, vol. 17(24), pages 1-22, December.
    2. Wei He & Wenhui Zhang & Zhenhua Chu & Yu Li, 2021. "Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques," IJERPH, MDPI, vol. 18(9), pages 1-19, May.
    3. Henrieta Hlisníková & Ida Petrovičová & Branislav Kolena & Miroslava Šidlovská & Alexander Sirotkin, 2020. "Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review," IJERPH, MDPI, vol. 17(18), pages 1-37, September.
    4. Fenglei Li & Qiaoyu Hu & Xianglei Zhang & Renhong Sun & Zhuanghua Liu & Sanan Wu & Siyuan Tian & Xinyue Ma & Zhizhuo Dai & Xiaobao Yang & Shenghua Gao & Fang Bai, 2022. "DeepPROTACs is a deep learning-based targeted degradation predictor for PROTACs," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Haigang Zhang & Chengji Zhao & Hui Na, 2020. "Enhanced Biodegradation of Phthalic Acid Esters’ Derivatives by Plasticizer-Degrading Bacteria ( Burkholderia cepacia , Archaeoglobus fulgidus , Pseudomonas aeruginosa ) Using a Correction 3D-QSAR Mod," IJERPH, MDPI, vol. 17(15), pages 1-17, July.
    6. Yilin Hou & Yuanyuan Zhao & Yu Li, 2020. "Environmentally Friendly Fluoroquinolone Derivatives with Lower Plasma Protein Binding Rate Designed Using 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation," IJERPH, MDPI, vol. 17(18), pages 1-18, September.
    7. Arathi Radhakrishnan & Pandiyan Balaganesh & Mangottiri Vasudevan & Narayanan Natarajan & Abhishek Chauhan & Jayati Arora & Anuj Ranjan & Vishnu D. Rajput & Svetlana Sushkova & Tatiana Minkina & Rupes, 2023. "Bioremediation of Hydrocarbon Pollutants: Recent Promising Sustainable Approaches, Scope, and Challenges," Sustainability, MDPI, vol. 15(7), pages 1-18, March.
    8. Michele Samorani & Manuel Laguna & Robert Kirk DeLisle & Daniel C. Weaver, 2011. "A Randomized Exhaustive Propositionalization Approach for Molecule Classification," INFORMS Journal on Computing, INFORMS, vol. 23(3), pages 331-345, August.
    9. Yuting Chen & Yuying Dong & Le Li & Jian Jiao & Sitong Liu & Xuejun Zou, 2022. "Toxicity Rank Order (TRO) As a New Approach for Toxicity Prediction by QSAR Models," IJERPH, MDPI, vol. 20(1), pages 1-10, December.
    10. Łukasz Sikorski & Agnieszka Bęś & Kazimierz Warmiński, 2023. "The Effect of Quinolones on Common Duckweed Lemna minor L., a Hydrophyte Bioindicator of Environmental Pollution," IJERPH, MDPI, vol. 20(6), pages 1-17, March.
    11. Xueyan Chen & Ugur Uzuner & Man Li & Weibing Shi & Joshua S. Yuan & Susie Y. Dai, 2016. "Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α," IJERPH, MDPI, vol. 13(9), pages 1-14, August.
    12. Benjamin M. Steiner & Abigail M. Benvie & Derek Lee & Yuwei Jiang & Daniel C. Berry, 2024. "Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:gam:jijerp:v:18:y:2021:i:20:p:10610-:d:653108. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: MDPI Indexing Manager (email available below). General contact details of provider: https://www.mdpi.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.