{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T08:07:23Z","timestamp":1783843643430,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304272"],"award-info":[{"award-number":["82304272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    Antimicrobial resistance (AMR) poses a significant global public health challenge. Vancomycin and \u03b2\u2010lactam antibiotics, critical for treating multidrug\u2010resistant (MDR) bacterial infections, are hindered by resistant strains such as vancomycin\u2010resistant\n                    <jats:italic>Enterococci<\/jats:italic>\n                    (VRE) and vancomycin\u2010intermediate\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , as well as \u03b2\u2010lactamase\u2010mediated resistance. This article leverages the complementary mechanisms of these antibiotics, which target bacterial cell wall synthesis, to develop vancomycin\u2010\u03b2\u2010lactam hybrids as a novel strategy against AMR. Through chemical modification, \u03b2\u2010lactam fragments were introduced at the carboxyl (C), resorcinol (R), and amine (N) termini of vancomycin, yielding multiple hybrid series. In vitro activity assays revealed that C\u2010terminal modified vancomycin\u2013penicillin hybrids exhibited superior efficacy, with compound\n                    <jats:bold>6a\u20136g<\/jats:bold>\n                    reducing the minimum inhibitory concentration against strains such as VREs by 512\u20131024\u2010fold compared to vancomycin, achieving activity comparable to oritavancin in certain strains. In vitro safety evaluations demonstrated low cytotoxicity of\n                    <jats:bold>6a<\/jats:bold>\n                    against human kidney (HK2) and embryonic kidney (HEK293) cell lines. These findings establish\n                    <jats:bold>6a<\/jats:bold>\n                    as a promising drug candidate, offering a novel therapeutic option for MDR infections.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501084","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:59:52Z","timestamp":1774544392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Vancomycin\u2010\u03b2\u2010Lactam Hybrids: Structure\u2013Activity Relationships and Therapeutic Potential Against VISA and VRE"],"prefix":"10.1002","volume":"21","author":[{"given":"Taopeng","family":"Chang","sequence":"first","affiliation":[{"name":"Anhui University of Chinese Medicine  Hefei China"},{"name":"Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery  Yantai Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-9221","authenticated-orcid":false,"given":"Chengtao","family":"Feng","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7697-5220","authenticated-orcid":false,"given":"Xiaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery  Yantai Shandong China"},{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Pudong, Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-1116","authenticated-orcid":false,"given":"Dongliang","family":"Guan","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery  Yantai Shandong China"},{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Pudong, Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_10_3_1","author":"O\u2019neill J. 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