{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:36:57Z","timestamp":1791549417339,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","award":["\u201cDiamond Grant\u201d no 0169\/DIA\/2017\/46"],"award-info":[{"award-number":["\u201cDiamond Grant\u201d no 0169\/DIA\/2017\/46"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N42\/DBS\/000070"],"award-info":[{"award-number":["N42\/DBS\/000070"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N42\/DBS\/000027"],"award-info":[{"award-number":["N42\/DBS\/000027"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N42\/DBS\/000093"],"award-info":[{"award-number":["N42\/DBS\/000093"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N42\/DBS\/000165 and N42\/DBS\/000162"],"award-info":[{"award-number":["N42\/DBS\/000165 and N42\/DBS\/000162"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015077","name":"Wydzia\u0142 Lekarski, Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N42\/DBS\/000096"],"award-info":[{"award-number":["N42\/DBS\/000096"]}],"id":[{"id":"10.13039\/100015077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7\u201323) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14\u201316 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7\u201323 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal \u201cdual action\u201d for \u03b2-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro.<\/jats:p>","DOI":"10.3390\/ijms22042062","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T20:54:08Z","timestamp":1613768048000},"page":"2062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria"],"prefix":"10.3390","volume":"22","author":[{"given":"Aneta","family":"Kaczor","sequence":"first","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, ul. 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