Li Xinao, Hou Yilin, Li Qing, Gu Wenwen, Li Yu
College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China; MOE Key Laboratory of Resources and Environmental System Optimization, North China Electric Power University, Beijing, 102206, China.
J Environ Manage. 2021 Dec 1;299:113628. doi: 10.1016/j.jenvman.2021.113628. Epub 2021 Aug 27.
The present study attempted to improve the biodegradation removal rate of Fluoroquinolones (FQs) in sewage treatment plants. The similarity index analysis (CoMSIA) model for combined biodegradability was constructed, and 33 kinds of molecular derivatives of FQs suitable for a variety of aerobic biodegradation microorganisms were designed. Further, derivative-20 and derivative-28, with high drug efficiency, drug safety, and environmental friendliness were selected through pharmacokinetics (ADMET), toxicokinetics (TOPKAT), FQs functional characteristics, and environmental friendliness evaluations. Compared with the target molecules, the combined biodegradability of the above two FQ-derivative molecules were increased by 193.57 % and 205.07 %, respectively, while their environment-friendly characteristics were improved to a certain degree. Through molecular docking and molecular dynamic simulation analysis, it showed that van der Waals force (decreased by 2.73 %-61.74 %) was the main factor influencing the binding ability of the modified FQ molecules to the receptor proteins. In addition, the relationship among the non-bonding interaction resultant force, the binding effect of the FQ-derivative molecules, and the receptor protein-related amino acid residues were studied for the first time. It was observed that the higher the value of the non-bonding interaction resultant force, the better was the binding effect, which demonstrating the significantly improved biodegradability of the designed FQ-derivative molecules.
本研究试图提高污水处理厂中氟喹诺酮类药物（FQs）的生物降解去除率。构建了联合生物降解性的相似性指数分析（CoMSIA）模型，并设计了33种适用于多种好氧生物降解微生物的FQs分子衍生物。此外，通过药代动力学（ADMET）、毒代动力学（TOPKAT）、FQs功能特性和环境友好性评估，筛选出了具有高药效、高药物安全性和环境友好性的衍生物-20和衍生物-28。与目标分子相比，上述两种FQ衍生物分子的联合生物降解性分别提高了193.57%和205.07%，同时其环境友好特性也有一定程度的改善。通过分子对接和分子动力学模拟分析表明，范德华力（降低了2.73%-61.74%）是影响修饰后的FQ分子与受体蛋白结合能力的主要因素。此外，首次研究了非键相互作用合力、FQ衍生物分子的结合效果与受体蛋白相关氨基酸残基之间的关系。结果表明，非键相互作用合力值越高，结合效果越好，这表明所设计的FQ衍生物分子的生物降解性显著提高。
