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

Designing and screening of fluoroquinolone substitutes using combined in silico approaches: biological metabolism–bioconcentration bilateral selection and their mechanism analyses

“…The genotoxicity HQSAR model 51 and the aerobic biodegradability 3D-QSAR model of FQs 31 were used to test the functional characteristics (genotoxicity) and environmental safety (biodegradability) of NOR substitute molecules, respectively. Screening NOR substitute molecules improved the functional characteristics and environmental safety (Table S3 †) (model prediction data are described in the ESI †).…”

“…30 In this study, 30 NOR substitute molecules were screened to meet the requirements of no reduction in genotoxicity (>5%) and significant enhancement in biodegradability (>25%), which were used as environment-friendly NOR substitute molecules with the enhanced bio-metabolic ability and reduced bio-concentration ability in aquatic organisms. Additionally, NOR and 30 substitute molecules were docked with three aerobic degrading enzymes of FQs (ID: 1B85, 1Q1R, and 5IDX) 31 for molecular docking, and an increase in the docking score was used as the basis for the universal evaluation of biodegradability of NOR substitute molecules. An increase in the scores of the modified NOR substitute molecules docking with 1B85, 1Q1R, and 5IDX were 76.67%, 96.67%, and 96.67%, respectively, which indicated that the designed NOR substitute molecules had good biodegradability.…”

“…An increase in the scores of the modified NOR substitute molecules docking with 1B85, 1Q1R, and 5IDX were 76.67%, 96.67%, and 96.67%, respectively, which indicated that the designed NOR substitute molecules had good biodegradability. 31 3.5. Drug characteristics, human health, and ecological risk evaluation of NOR substitutes based on ADMET and TOPKAT 3.5.1.…”

“…In particular, the genetic toxicity, 28 photodegradation, 29 biodegradability and spectral characteristics of FQs were studied by using single-effect or multiple-effects 3D-QSAR models of FQs. 30,31 However, the bidirectional selectivity of FQ bio-concentration and biometabolism has not been reported. Research on the combination of in silico techniques and target protein claims that in silico techniques such as molecular docking 32 and MD simulations 33 play a prominent role in the study of ligandreceptor protein interactions.…”

Bio-Enhanced Degradation Strategies for Fluoroquinolones in the Sewage Sludge Composting Stage: Molecular Modification and Resistance Gene Regulation

“…Fluoroquinolones (FQs), with better broad-spectrum and pharmacokinetics than the first generation of quinolones antibiotics, developed rapidly from 1970 to 1980 [1]. FQs are a class of synthetic broad-spectrum antibacterial agents, they are widely used in clinical treatment in hospitals and veterinary practices [2]. However, only a small fraction of FQs are absorbed by the organism.…”