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

Ecotoxicology and Environmental Safety

卷:212

Yu Li¹  Wenwen Gu²  Ruihao Sun²  Wenhui Zhang²  Mengying Zhou²  Zhenzhen Han² 

[1] Corresponding author.;

[2] The Key Laboratory of Resource and Environmental System Optimization, Ministry of Education, North China Electric Power University, Beijing 102206, China;

关键词: Multi-index comprehensive weighted score evaluation;    Gatifloxacin;    Photodegradation or microbial degradation of fluoroquinolone;    Combined degradation effect;    Molecular modification;    Potential environmental risks;   

DOI  :  

来源: DOAJ

【 摘 要 】

This study developed a comprehensive characterization method for the combined degradation effect of modified fluoroquinolones (FQs) photodegradation and microbial degradation. A combination of revised 3D-QSAR model, molecular docking, path simulation inference, pharmacokinetics, molecular dynamics (MD) simulation and toxicokinetics simulation was used to construct a systematic environment-friendly drug screening system. Five derivatives were screened with significantly improved combined degradation effect (over 20%) and functional characteristics and human health parameters through combined model verification, functional and human health risk assessment. The simulation path of photo- and microbial-degradation of gatifloxacin and new gatifloxacin molecules was derived, and the reaction energy barrier was also calculated. The ratio of the total rate-determining steps change rate of the decreased energy barrier (14.10%:26.30%) was consistent with the ratio of the increased degradation performance predicted by the model (22.87%:19.77%), demonstrating the reliability of revised 3D-QSAR model and it could be applied in molecular modification. MD and toxicokinetics simulation were used to predict the binding energy and aquatic toxicity between photo- and microbial-degradation products and the degradation enzymes, which further to screen the degradation pathways with low potential environmental risks. The findings will be helpful to screen environment-friendly drug and develop appropriate strategies for its risk management.

【 授权许可】

Unknown