{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:35Z","timestamp":1787028455614,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2015\/17\/B\/ST5\/00076"],"award-info":[{"award-number":["UMO-2015\/17\/B\/ST5\/00076"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019771","name":"Rega Foundation","doi-asserted-by":"publisher","award":["Rega Foundation"],"award-info":[{"award-number":["Rega Foundation"]}],"id":[{"id":"10.13039\/501100019771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009045","name":"Jagiellonian University Medical College","doi-asserted-by":"publisher","award":["N42\/DBS\/000196"],"award-info":[{"award-number":["N42\/DBS\/000196"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A novel series of N-substituted cis- and trans-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3\u2013H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one trans-11f showed moderate inhibitory activity against human coronavirus (229E) with EC50 = 45 \u00b5M. The other isomer cis-11f was active against influenza A virus H1N1 subtype (EC50 = 12 \u00b5M by visual CPE score; EC50 = 8.3 \u00b5M by TMS score; MCC &gt; 100 \u00b5M, CC50 = 39.9 \u00b5M). Several azetidin-2-ones 10 and 11 were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC50 in the range 14.5\u201397.9 \u00b5M. Compound trans-11f was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant S. aureus strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3R,4S)-11f can be responsible for the promising activity due to the potency in displacing oxacillin at \u03b2-lactamase, thus protecting the antibiotic from undesirable biotransformation.<\/jats:p>","DOI":"10.3390\/ijms22158032","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"8032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7567-5860","authenticated-orcid":false,"given":"Iwona E.","family":"G\u0142owacka","sequence":"first","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4230-0218","authenticated-orcid":false,"given":"Magdalena","family":"Grabkowska-Dru\u017cyc","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-4896","authenticated-orcid":false,"given":"Graciela","family":"Andrei","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, Box 1030, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-5850","authenticated-orcid":false,"given":"Dominique","family":"Schols","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, Box 1030, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Snoeck","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Herestraat 49, Box 1030, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Witek","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Krakow, Poland"}],"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, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Krakow, Poland"},{"name":"Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, ul. Sm\u0119tna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3674-3581","authenticated-orcid":false,"given":"Jadwiga","family":"Handzlik","sequence":"additional","affiliation":[{"name":"Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3792-8796","authenticated-orcid":false,"given":"Dorota G.","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","first-page":"226","article-title":"On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of b. influenza","volume":"10","author":"Fleming","year":"1929","journal-title":"Br. J. Exp. 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