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Due to its efficient molecular structure and synthetic usability due to the alcohol group in its framework, medicinal chemists aimed to reach new more effective molecules such as MTZ\u2010hybrids. In this study, 2\u2010[(benzimidazole\/benzoxazole\/benzothiazol\u20102\u2010yl)thio]\u2010<jats:italic>N<\/jats:italic>\u2010[2\u2010(2\u2010methyl\u20105\u2010nitro\u20101<jats:italic>H<\/jats:italic>\u2010imidazol\u20101\u2010yl)ethyl]acetamide (<jats:bold>5a\u22125j<\/jats:bold>) derivatives were synthesized and their antimicrobial and antifungal effects on aerobic bacteria and <jats:italic>Candida<\/jats:italic> spp. were investigated. Notably, most of newly designed conjugates displayed higher potency than MTZ itself, especially against Gram\u2010positive strains. Furthermore, chlorinated heterocyclic moieties provided the strongest effects. Docking studies using <jats:italic>E. coli<\/jats:italic> nitroreductase (PDB: 1IDT) revealed potential interactions with the flavin mononucleotide (FMN) cofactor, suggesting that these hybrids may undergo nitro\u2010group reduction analogous to MTZ. Additionally, pharmacokinetic predictions indicated generally favorable profiles.<\/jats:p>","DOI":"10.1002\/ddr.70114","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:54:56Z","timestamp":1749534896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Metronidazole Conjugates as Antimicrobial Agents"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-6157","authenticated-orcid":false,"given":"Erol","family":"Akg\u00fcn","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Marmara University \u0130stanbul T\u00fcrkiye"},{"name":"Department of Pharmaceutical Chemistry, Institute of Graduate Education Anadolu University Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"Demirayak","sequence":"additional","affiliation":[{"name":"\u0130nci Dental Polyclinic Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-6044","authenticated-orcid":false,"given":"Leyla","family":"Yurtta\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Anadolu University Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-1633","authenticated-orcid":false,"given":"\u00dclkiye Dudu","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Faculty of Engineering Bilecik \u015eeyh Edebali University Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-1299","authenticated-orcid":false,"given":"\u015eeref","family":"Demirayak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy \u0130stanbul Okan University \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-011-9689-y"},{"issue":"3","key":"e_1_2_8_3_1","first-page":"156","article-title":"1\u2010[2\u2010Substituted Ethyl]\u20102\u2010Methyl\u20105\u2010Nitroimidazole Derivatives, Synthesis and Antibacterial Activities","volume":"5","author":"Al\u2010Sha'er M. 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