{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:39:47Z","timestamp":1790732387553,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The epidemic of multidrug resistance (MDR) is a serious threat to public health, and new classes of antibiotics with novel mechanisms of action are in critical need. We rationally designed and efficiently synthesized three series of new chemical entities with potential antibacterial activity targeting filamenting temperature\u2010sensitive mutant Z (FtsZ). Evaluation of these compounds against a panel of Gram\u2010positive bacteria including MDR and vancomycin\u2010resistant <jats:italic>Enterococcus<\/jats:italic>\u00a0strains indicated that most compounds showed enhanced antibacterial efficacy, comparable or even superior to the reference drugs. The newly synthesized compounds proved to be substrates of the <jats:italic>Escherichia coli<\/jats:italic> efflux pump AcrB, thus affecting the activity. Their structure\u2013activity relationships\u00a0were summarized in detail. The most potent compound <jats:bold>10f<\/jats:bold> quickly eliminated bacteria in a bactericidal mode, with low susceptibility to induce bacterial resistance. Further mechanistic studies with the <jats:italic>Bs<\/jats:italic>FtsZ protein revealed that <jats:bold>10f<\/jats:bold> functioned as an effective FtsZ inhibitor through altering the dynamics of FtsZ self\u2010polymerization via a stimulatory mechanism, which leads to inhibition of cell division and cell death. Besides, <jats:bold>10f<\/jats:bold> not only displayed no obvious cytotoxicity to mammalian cells but also had a high efficacy in a murine model of bacteremia in vivo. Regarded as a whole, our findings highlight <jats:bold>10f<\/jats:bold> as a promising new FtsZ\u2010targeting bactericidal agent.<\/jats:p>","DOI":"10.1002\/ardp.202100400","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T13:32:16Z","timestamp":1646919136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acridinium\u2010conjugated aromatic heterocycles as highly potent FtsZ inhibitors: Design, synthesis, and biological evaluation"],"prefix":"10.1002","volume":"355","author":[{"given":"Di","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University  Jinan Shandong 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