Scaffold Simplification Yields Potent Antibacterial Agents That Target Bacterial Topoisomerases.

ABSTRACT: This work describes the lead optimization of a promising class of antibacterial compounds, derived from a previously reported N-[4-(4-fluorophenoxy)phenyl]-6-(methylsulfonyl)-2,6-diazaspiro [3.4]octane-8-carboxamide (LK1819), through systematic scaffold simplification. A novel series of amide derivatives were designed and synthesized, exploring key structural variations, including the replacement of the diphenyl ether core with a biphenyl system. All compounds were evaluated for in vitro antibacterial activity against the ESKAPE panel of pathogens. The most potent simplified analogs demonstrated exceptional, broad-spectrum activity, with minimum inhibitory concentrations (MICs) that were 10 to 100 times lower than the control antibiotic ciprofloxacin against many strains. Mechanisti

SUBMITTER: Khudiakova L 

PROVIDER: S-EPMC12844012 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature