{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:43:23Z","timestamp":1784317403568,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GN1147538"],"award-info":[{"award-number":["GN1147538"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973179"],"award-info":[{"award-number":["81973179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673284)"],"award-info":[{"award-number":["81673284)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The bacterial cell division protein, FtsZ, has been identified as a target for antimicrobial development. Derivatives of 3-methoxybenzamide have shown promising activities as FtsZ inhibitors in Gram-positive bacteria. We sought to characterise the activity of five difluorobenzamide derivatives with non-heterocyclic substituents attached through the 3-oxygen. These compounds exhibited antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA), with an isopentyloxy-substituted compound showing modest activity against vancomycin resistant Enterococcus faecium (VRE). The compounds were able to reverse resistance to oxacillin in highly resistant clinical MRSA strains at concentrations far below their MICs. Three of the compounds inhibited an Escherichia coli strain lacking the AcrAB components of a drug efflux pump, which suggests the lack of Gram-negative activity can partly be attributed to efflux. The compounds inhibited cell division by targeting S. aureus FtsZ, producing a dose-dependent increase in GTPase rate which increased the rate of FtsZ polymerization and stabilized the FtsZ polymers. These compounds did not affect the polymerization of mammalian tubulin and did not display haemolytic activity or cytotoxicity. These derivatives are therefore promising compounds for further development as antimicrobial agents or as resistance breakers to re-sensitive MRSA to beta-lactam antibiotics.<\/jats:p>","DOI":"10.3390\/antibiotics9120873","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T22:27:12Z","timestamp":1607293632000},"page":"873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antimicrobial Action and Reversal of Resistance in MRSA by Difluorobenzamide Derivatives Targeted at FtsZ"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-4341","authenticated-orcid":false,"given":"Wern Chern","family":"Chai","sequence":"first","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Whittall","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-5194","authenticated-orcid":false,"given":"Steven W.","family":"Polyak","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-5629","authenticated-orcid":false,"given":"Abiodun D.","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Australia Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy Campus, SA 5371 Roseworthy, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"},{"name":"School of Pharmacy, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangchao","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1206-2375","authenticated-orcid":false,"given":"Shutao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5988-3993","authenticated-orcid":false,"given":"Susan J.","family":"Semple","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"},{"name":"Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7755","authenticated-orcid":false,"given":"Henrietta","family":"Venter","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, SA 5000 Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","unstructured":"O\u2019Neill, J. 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