{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:30:51Z","timestamp":1791189051546,"version":"4.1.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The type II topoisomerases DNA gyrase (GyrA\/GyrB) and topoisomerase IV (ParC\/ParE) are well-validated targets for antibacterial drug discovery. Because of their structural and functional homology, these enzymes are amenable to dual targeting by a single ligand. In this study, two novel benzothiazole ethyl urea-based small molecules, designated compound A and compound B, were evaluated for their biochemical, antibacterial, and pharmacokinetic properties. The two compounds inhibited the ATPase activity of GyrB and ParE with 50% inhibitory concentrations of &lt;0.1 \u03bcg\/ml. Prevention of DNA supercoiling by DNA gyrase was also observed. Both compounds potently inhibited the growth of a range of bacterial organisms, including staphylococci, streptococci, enterococci,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Clostridium difficile<\/jats:named-content>\n            , and selected Gram-negative respiratory pathogens. MIC\n            <jats:sub>90<\/jats:sub>\n            s against clinical isolates ranged from 0.015 \u03bcg\/ml for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            to 0.25 \u03bcg\/ml for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            . No cross-resistance with common drug resistance phenotypes was observed. In addition, no synergistic or antagonistic interactions between compound A or compound B and other antibiotics, including the topoisomerase inhibitors novobiocin and levofloxacin, were detected in checkerboard experiments. The frequencies of spontaneous resistance for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            were &lt;2.3 \u00d7 10\n            <jats:sup>\u221210<\/jats:sup>\n            with compound A and &lt;5.8 \u00d7 10\n            <jats:sup>\u221211<\/jats:sup>\n            with compound B at concentrations equivalent to 8\u00d7 the MICs. These values indicate a multitargeting mechanism of action. The pharmacokinetic properties of both compounds were profiled in rats. Following intravenous administration, compound B showed approximately 3-fold improvement over compound A in terms of both clearance and the area under the concentration-time curve. The measured oral bioavailability of compound B was 47.7%.\n          <\/jats:p>","DOI":"10.1128\/aac.00719-13","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T03:45:54Z","timestamp":1379389554000},"page":"5977-5986","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Biological Evaluation of Benzothiazole Ethyl Urea Inhibitors of Bacterial Type II Topoisomerases"],"prefix":"10.1128","volume":"57","author":[{"given":"Neil R.","family":"Stokes","sequence":"first","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena B.","family":"Thomaides-Brears","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Barker","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Berry","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Collins","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd G.","family":"Czaplewski","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Gamble","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lancett","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair","family":"Logan","sequence":"additional","affiliation":[{"name":"Biota Europe Ltd., Begbroke, Oxfordshire, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Lunniss","sequence":"additional","affiliation":[{"name":"Biota Scientific Management Pty. 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