Novel fluoroquinolone-based organic salts: Pioneering solutions in targeting bacterial DNA gyrase

• Novel fluoroquinolone-based GUMBOS were created and structurally characterized. • Effect of different structures of FQs and anions on E. coli DNA gyrase activity. • Antibacterial profiles and IC 50 values of GUMBOS targeting DNA gyrase. • Ciprofloxacin-based GUMBOS exhibited decreased IC 50 values (0.106–1.084 µM). • [Mox][NTF 2 ] demonstrated the highest inhibition effect (IC 50 0.076 µM). Antimicrobial resistance presents itself as a serious hazard to public global health, thus emphasizing the need for alternative drugs. Innovative approaches include a group of uniform materials based on organic salts (GUMBOS) which resemble ionic liquids in their tunability abilities. Thus, changing ionic counterparts, several novel fluoroquinolone-based GUMBOS were created. DNA gyrase is a known target for drug development as it is essential for bacterial DNA replication. Using a high-throughput screening (HTS) assay, the new GUMBOŚs antibacterial profiles were traced, and half-maximal inhibitory concentration (IC 50 ) values were calculated. Ciprofloxacin ([Cip]), lomefloxacin ([Lom]), and moxifloxacin ([Mox])-based GUMBOS were synthesized and structurally characterized. Then, the cationic or anionic counterparts’ influence on DNA gyrase’s activity or inhibition was evaluated and compared with clinical precursors. Anion choice was fundamental to improve inhibitory effects. All [Cip]-based GUMBOS exhibited improved IC 50 values (IC 50 0.106–1.084 µM) outperforming ciprofloxacin. Among [Lom]-based GUMBOS, only [Lom][NTF 2 ] and [Lom][Dxc] showed improved inhibition over lomefloxacin. [Mox]-based GUMBOS generally had higher inhibitory effects than moxifloxacin, with [Mox][NTF 2 ] exhibiting the highest inhibition effect of all GUMBOS (IC 50 0.076 µM). Overall, most GUMBOS exhibited an inhibitory profile towards DNA gyrase, revealing the potential to be further researched and used in the clinic as antimicrobial agents.