{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T14:48:43Z","timestamp":1779374923958,"version":"3.53.1"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,26]],"date-time":"2019-01-26T00:00:00Z","timestamp":1548460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Ministry of Science","award":["0169\/DIA\/2017\/46"],"award-info":[{"award-number":["0169\/DIA\/2017\/46"]}]},{"name":"National Statutory Research Project","award":["K\/ZDS\/007886"],"award-info":[{"award-number":["K\/ZDS\/007886"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Searching for new chemosensitizers of bacterial multidrug resistance (MDR), chemical modifications of (Z)-5-(4-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-3H-imidazol-4(5H)-one (6) were performed. New compounds (7\u201317), with fused aromatic rings at position 5, were designed and synthesized. Crystallographic X-ray analysis proved that the final compounds (7\u201317) were substituted with tertiary amine-propyl moiety at position 3 and primary amine group at 2 due to intramolecular Dimroth rearrangement. New compounds were evaluated on their antibiotic adjuvant properties in either Gram-positive or Gram-negative bacteria. Efflux pump inhibitor (EPI) properties towards the AcrAB-TolC pump in Enterobacter aerogenes (EA289) were investigated in the real-time efflux (RTE) assay. Docking and molecular dynamics were applied to estimate an interaction of compounds 6\u201317 with penicillin binding protein (PBP2a). In vitro ADME-Tox properties were evaluated for compound 9. Most of the tested compounds reduced significantly (4-32-fold) oxacillin MIC in highly resistant MRSA HEMSA 5 strain. The anthracene-morpholine derivative (16) was the most potent (32-fold reduction). The tested compounds displayed significant EPI properties during RTE assay (37\u201397%). The naphthyl-methylpiperazine derivative 9 showed the most potent \u201cdual action\u201d of both oxacillin adjuvant (MRSA) and EPI (E. aerogenes). Molecular modeling results suggested the allosteric mechanism of action of the imidazolones, which improved binding of oxacillin in the PBP2a active site in MRSA.<\/jats:p>","DOI":"10.3390\/molecules24030438","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T03:40:55Z","timestamp":1548733255000},"page":"438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["5-Arylideneimidazolones with Amine at Position 3 as Potential Antibiotic Adjuvants against Multidrug Resistant Bacteria"],"prefix":"10.3390","volume":"24","author":[{"given":"Aneta","family":"Kaczor","sequence":"first","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Witek","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"},{"name":"Department of Pharmaceutical Microbiology; Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"},{"name":"Aix Marseille Univ, INSERM, SSA, MCT, FAC PHARM, 27 Bd Jean Moulin, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-5603","authenticated-orcid":false,"given":"Sabina","family":"Podlewska","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"},{"name":"Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, 31-343 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Czekajewska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology; Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Lubelska","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-9370","authenticated-orcid":false,"given":"Ewa","family":"\u017bes\u0142awska","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Biology, Pedagogical University of Cracow, Podchor\u0105\u017cych 2, 30-084 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Nitek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-2598","authenticated-orcid":false,"given":"Gniewomir","family":"Latacz","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5811-0139","authenticated-orcid":false,"given":"Sandrine","family":"Alibert","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, SSA, MCT, FAC PHARM, 27 Bd Jean Moulin, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Pag\u00e8s","sequence":"additional","affiliation":[{"name":"Aix Marseille Univ, INSERM, SSA, MCT, FAC PHARM, 27 Bd Jean Moulin, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Karczewska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology; Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kie\u0107-Kononowicz","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadwiga","family":"Handzlik","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tanwar, J., Das, S., Fatima, Z., and Hameed, S. 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