Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents.

摘要: Abstract A series of novel fluoroquinolone-Safirinium dye hybrids was synthesized by means tandem Mannich-electrophilic amination reactions from profluorophoric isoxazolones and antibiotics bearing a secondary amino group at position 7 the quinoline ring. The obtained fluorescent spiro fused conjugates incorporating quaternary nitrogen atoms were characterized 1H NMR, IR, MS, elemental analysis. All synthetic analogues (3a-h 4a-h) evaluated for their in vitro antimicrobial, bactericidal, antibiofilm activities against panel Gram positive Gram-negative pathogenic bacteria. most active Safirinium Q derivatives lomefloxacin (4d) ciprofloxacin (4e) exhibited molar-based antibacterial comparable to unmodified drugs displayed considerable inhibitory potencies in E. coli DNA gyrase supercoiling assays with IC50 values low micromolar range. Zwiterionic noticeably less lipophilic than parent quinolones micellar electrokinetic chromatography (MECK) experiments. tests performed presence phenylalanine-arginine β-naphthylamide (PAβN) or carbonyl cyanide m-chlorophenylhydrazone (CCCP) revealed that are some extent subject bacterial efflux cellular accumulation, respectively. Moreover, did not exhibit notable cytotoxicity towards HEK 293 control cell line demonstrated propensity resistance development, as exemplified compounds 3g 4b. Finally, molecular docking experiments able bind fluoroquinolone-binding mode S. aureus S. pneumoniae topoisomerase IV sites.