Nigiz Ş.Kulabaş N.Türe A.Kablan S.Koçak E.Özkul C.Küçükgüzel İ.2026-03-122026-03-1220260269-387910.1002/bmc.704072-s2.0-105030628707https://doi.org/10.1002/bmc.70407https://hdl.handle.net/20.500.14627/1462Antimicrobial resistance is one of the most important global problems, and new antibiotic requirements have been emerging as a key point in this issue. In the present work, we focused on the efficiency of two novel promising fluoroquinolone derivatives on resistant Escherichia coli isolates at the molecular level. Their mode of action and adaptation process were evaluated by using proteomics and metabolomics analysis. Proteomics analysis showed that two compounds have an effect mainly on the ribosomal process and energy metabolism. Moreover, we observed compounds that affect various important antimicrobial targets, such as ribosomal subunits, phosphotransacetylase, and chaperone proteins. In metabolomics analysis, we found that compounds altered bacterial metabolism directly. Pathway analysis showed that cofactor biosynthesis and energy metabolism were affected mainly by undertreated groups. Our experiments demonstrated that novel fluoroquinolone derivatives have promising results at the molecular level and results will contribute to further studies. © 2026 John Wiley & Sons Ltd.eninfo:eu-repo/semantics/openAccessAntibacterialsEscherichia ColiFluoroquinolonesMetabolomicsProteomicsArticle