Synthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivativessynthesis, Antibacterial Evaluation and in Silico Study of DOTA-fluoroquinolone Derivatives
Abstract A series of water-soluble fluoroquinolones based upon DOTA modification were synthesized and characterized by NMR and HRMS spectra. All the newly prepared quinolones compounds exhibited potent antimicrobial activities against MRSA, P. aeruginosa and E. coli. Molecular docking study indicated they could form stable complex with DNA gyrase and topoisomerase IV-DNA respectively, ADMET prediction showed they were low toxicity to the mice as whole. Among them, water-soluble quinolone 4c exhibited promising antibacterial potency, its MIC, MBC value for MRSA and P. aeruginosa was (1.56, 6.25) µg/mL, (3.1, 12.5) µg/mL respectively. Atomic Force Microscope (AFM) imaging revealed 4c could effectively destroy MRSA bacterial membrane and wall, causing its contents to leak out. Cytotoxicity assay showed 4c had low toxicity to L-02, A549 and MCF-7, over 80% cell viability even at 100 µmol/L. These results showed that water-soluble compound 4c was a promising antibacterial candidate.