{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:58:39Z","timestamp":1790261919700,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["No. 2019YJ0454"],"award-info":[{"award-number":["No. 2019YJ0454"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Education Department","award":["No. 18TD0023"],"award-info":[{"award-number":["No. 18TD0023"]}]},{"name":"Chunhui of Ministry of Education Project","award":["No. Z2017062"],"award-info":[{"award-number":["No. Z2017062"]}]},{"name":"Young Scholars Reserve Talents program of Xihua University","award":["No. 0220170305"],"award-info":[{"award-number":["No. 0220170305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The emergence and spread of metallo-\u03b2-lactamase (MBL)-mediated resistance to \u03b2-lactam antibacterials has already threatened the global public health. A clinically useful MBL inhibitor that can reverse \u03b2-lactam resistance has not been established yet. We here report a series of [1,2,4]triazole derivatives and analogs, which displayed inhibition to the clinically relevant subclass B1 (Verona integron-encoded MBL-2) VIM-2. 3-(4-Bromophenyl)-6,7-dihydro-5H-[1,2,4]triazolo [3,4-b][1,3]thiazine (5l) manifested the most potent inhibition with an IC50 (half-maximal inhibitory concentration) value of 38.36 \u03bcM. Investigations of 5l against other B1 MBLs and the serine \u03b2-lactamases (SBLs) revealed the selectivity to VIM-2. Molecular docking analyses suggested that 5l bound to the VIM-2 active site via the triazole involving zinc coordination and made hydrophobic interactions with the residues Phe61 and Tyr67 on the flexible L1 loop. This work provided new triazole-based MBL inhibitors and may aid efforts to develop new types of inhibitors combating MBL-mediated resistance.<\/jats:p>","DOI":"10.3390\/molecules25010056","type":"journal-article","created":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T05:56:15Z","timestamp":1577166975000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Discovery of [1,2,4]Triazole Derivatives as New Metallo-\u03b2-Lactamase Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"given":"Chen","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Song","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Su","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Science, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Qian","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/S1473-3099(14)70780-7","article-title":"Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data","volume":"14","author":"Gandra","year":"2014","journal-title":"Lancet Infect. 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