{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:26:47Z","timestamp":1787765207175,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of hybridized pyrrolidine compounds with a 1,2,4\u2010oxadiazole moiety were synthesized to develop effective molecules against the enzymes DNA gyrase and topoisomerase IV (Topo IV). Compounds <jats:bold>8\u201320<\/jats:bold> were developed based on a previously disclosed series of compounds from our lab, but with small structural modifications in the hopes of increasing the compounds' biological activity. In comparison to novobiocin, with IC<jats:sub>50<\/jats:sub>\u2009=\u2009170\u2009nM, the findings of the DNA gyrase inhibitory assay revealed that compounds <jats:bold>16<\/jats:bold> and <jats:bold>17<\/jats:bold> were the most potent of all synthesized derivatives, with IC<jats:sub>50<\/jats:sub> values of 180 and 210\u2009nM, respectively. Compound <jats:bold>17<\/jats:bold> had the strongest inhibitory effect against <jats:italic>Escherichia coli<\/jats:italic> Topo IV of all the synthesized compounds, with an IC<jats:sub>50<\/jats:sub> value of 13\u2009\u00b5M, which was comparable to novobiocin (IC<jats:sub>50<\/jats:sub>\u2009=\u200911\u2009\u00b5M). Therefore, hybrids <jats:bold>16<\/jats:bold> and <jats:bold>17<\/jats:bold> appeared to be potential dual\u2010target inhibitors. In the minimal inhibitory concentration (MIC) assays, compound <jats:bold>17<\/jats:bold> outperformed ciprofloxacin against <jats:italic>E. coli<\/jats:italic>, with an MIC of 55\u2009ng\/ml, compared to 60\u2009ng\/ml for ciprofloxacin. Finally, the docking study, along with the in vitro experiments, supports our promising approach to effectively develop potent leads for further optimization as dual DNA gyrase and Topo IV inhibitors.<\/jats:p>","DOI":"10.1002\/ardp.202100516","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T13:34:01Z","timestamp":1648820041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["New 1,2,4\u2010oxadiazole\/pyrrolidine hybrids as topoisomerase IV and DNA gyrase inhibitors with promising antibacterial activity"],"prefix":"10.1002","volume":"355","author":[{"given":"Firas O. A.","family":"Frejat","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Technology of Drug Preparation (Zhengzhou University) Ministry of Education of China  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaquan","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Technology of Drug Preparation (Zhengzhou University) Ministry of Education of China  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Technology of Drug Preparation (Zhengzhou University) Ministry of Education of China  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjin","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhengzhou University  Zhengzhou People's Republic of China"},{"name":"Key Laboratory of Technology of Drug Preparation (Zhengzhou University) Ministry of Education of China  Zhengzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Abdelazeem","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"},{"name":"Pharmacy Department, College of Pharmacy Riyadh Elm University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham A. 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