Molecular design of high-efficacy and high drug safety Fluoroquinolones suitable for a variety of aerobic biodegradation bacteria

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. [Display omitted] •Biodegradability of 33 compounds were analyzed with 3D-QSAR method.•Toxicokinetics and pharmacokinetics were used to screen high efficacy and safety.•The Derivative-20 and 28 screened had higher biodegradability than levofloxacin.•Mechanism analysis based on Molecular docking, Molecular dynamic and Resultant force.