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The World Health Organization has ranked fluoroquinolone-resistant\n            <jats:italic>Salmonella<\/jats:italic>\n            as a high-priority pathogen for researching and developing new antibiotics. WQ-3034 and WQ-3154 are relatively new synthetic fluoroquinolones with distinctive structures. WQ-3034 has 6-amino-3,5-difluoropyridine-2-yl at R\n            <jats:sub>1<\/jats:sub>\n            , 3-hydroxyazetidinyl at R\n            <jats:sub>7<\/jats:sub>\n            , and the addition of chlorine atom at R\n            <jats:sub>8<\/jats:sub>\n            . WQ-3154 has a similar basic pharmacophore to WQ-3034 except for the modification at R\n            <jats:sub>8<\/jats:sub>\n            with a methyl group. In this study, the inhibitory effect and DNA cleavage effect against wild-type (WT) and mutant\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium DNA gyrases of WQ-3034 and WQ-3154 were examined along with WQ-3810 and ciprofloxacin by measuring the drug concentration that inhibits half of the enzyme activity (IC\n            <jats:sub>50<\/jats:sub>\n            ) and the drug concentration that induces 25% of maximum DNA cleavage (CC\n            <jats:sub>25<\/jats:sub>\n            ). The minimum inhibitory concentration (MIC) of the compounds was assessed against\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium and\n            <jats:italic>Salmonella<\/jats:italic>\n            Enteritidis. Among four compounds, WQ-3034 demonstrated the highest inhibitory effect against both WT and mutant\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium DNA gyrases with amino acid substitution at codon 83 and\/or 87, while ciprofloxacin showed the lowest inhibitory effect. Remarkably, WQ-3034 and WQ-3154 exhibited a significantly higher inhibitory effect than ciprofloxacin against\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium DNA gyrase with double amino acid substitution, Ser83Phe-Asp87Asn. Similarly, CC\n            <jats:sub>25<\/jats:sub>\n            of WQ-3034 against mutant\n            <jats:italic>Salmonella<\/jats:italic>\n            Typhimurium DNA gyrase was lower than ciprofloxacin. Notably, MICs of WQ-3034 and WQ-3154 were higher than ciprofloxacin. In conclusion, this study revealed that WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant nontyphoidal\n            <jats:italic>Salmonella<\/jats:italic>\n            .\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Quinolone-resistant nontyphoidal\n              <jats:italic>Salmonella<\/jats:italic>\n              is a pressing public health concern, demanding the exploration of novel treatments. In this study, we focused on two innovative synthetic fluoroquinolones, WQ-3034 and WQ-3154. Our findings revealed that these new compounds demonstrate potent inhibitory effects, even against mutant strains that cause resistance to existing quinolones. Hence, WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant\n              <jats:italic>Salmonella<\/jats:italic>\n              Typhimurium. Furthermore, the data obtained in this study will be baseline information for antimicrobial drug development.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01330-23","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T13:02:04Z","timestamp":1696510924000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Exploration of the novel fluoroquinolones with high inhibitory effect against quinolone-resistant DNA gyrase of\n            <i>Salmonella<\/i>\n            Typhimurium"],"prefix":"10.1128","volume":"11","author":[{"given":"Jirachaya","family":"Toyting","sequence":"first","affiliation":[{"name":"Division of Bioresources, Hokkaido University International Institute for Zoonosis Control , Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nami","family":"Miura","sequence":"additional","affiliation":[{"name":"Division 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