Synthesis and in vitro antibacterial activity of a series of novel gatifloxacin derivatives

A series of novel gatifloxacin (GTFX) derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR, MS and HRMS. These derivatives were evaluated for in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Our results reveal that most of the target compounds show good potency in inhibiting the growth of Staphylococcus aureus including MRSA and Staphylococcus epidermidis including MRSE. Compounds 8, 14 and 20 have useful activity against all of the tested Gram-positive and Gram-negative strains (MICs: 0.06–4 μg/mL). In particular, 20 possessing a broad antimicrobial spectrum (MICs: 0.06–1 μg/mL) was found to be 2–32-folds more potent than the reference drug levofloxacin and parent GTFX against Pseudomonas aeruginosa.

Graphical abstractA series of novel gatifloxacin derivatives 1–21 were designed and synthesized. Most of the title compounds show good antibacterial activity against the representative Gram-positive and Gram-negative strains.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Most of 1–21 show good activity against S. aureus and S. epidermidis including MRSA and MRSE. ► 8, 14, 20 have useful activity against all of the tested strains (MICs: 0.06–4 μg/mL). ► 20 is 2–32-folds more potent than the references against P. aeruginosa (MICs: 0.25–0.5 μg/mL).