{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:57:05Z","timestamp":1790261825747,"version":"4.1.0"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["725523"],"award-info":[{"award-number":["725523"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the search for new inhibitors of bacterial metallo-\u03b2-lactamases (MBLs), a series of commonly used small molecule carboxylic acid derivatives were evaluated for their ability to inhibit New Delhi metallo-\u03b2-lactamase (NDM)-, Verona integron-encoded metallo-\u03b2-lactamase (VIM)-, and imipenemase (IMP)-type enzymes. Nitrilotriacetic acid (3) and N-(phosphonomethyl)iminodiacetic acid (5) showed promising activity especially against NDM-1 and VIM-2 with IC50 values in the low-to-sub \u03bcM range. Binding assays using isothermal titration calorimetry reveal that 3 and 5 bind zinc with high affinity with dissociation constant (Kd) values of 121 and 56 nM, respectively. The in vitro biological activity of 3 and 5 against E.\u00a0coli expressing NDM-1 was evaluated in checkerboard format, demonstrating a strong synergistic relationship for both compounds when combined with Meropenem. Compounds 3 and 5 were then tested against 35 pathogenic strains expressing MBLs of the NDM, VIM, or IMP classes. Notably, when combined with Meropenem, compounds 3 and 5 were found to lower the minimum inhibitory concentration (MIC) of Meropenem up to 128-fold against strains producing NDM- and VIM-type enzymes.<\/jats:p>","DOI":"10.1021\/acsinfecdis.9b00459","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T09:41:21Z","timestamp":1585647681000},"page":"1366-1371","source":"Crossref","is-referenced-by-count":26,"title":["Small Molecule Carboxylates Inhibit Metallo-\u03b2-lactamases\nand Resensitize Carbapenem-Resistant Bacteria to Meropenem"],"prefix":"10.1021","volume":"6","author":[{"given":"Kamaleddin H. M. E.","family":"Tehrani","sequence":"first","affiliation":[{"name":"Leiden University , , Sylviusweg 72 , ,","place":["Leiden, The Netherlands, 2333 BE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora C.","family":"Bru\u0308chle","sequence":"additional","affiliation":[{"name":"Leiden University , , Sylviusweg 72 , ,","place":["Leiden, The Netherlands, 2333 BE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Wade","sequence":"additional","affiliation":[{"name":"Leiden University , , Sylviusweg 72 , ,","place":["Leiden, The Netherlands, 2333 BE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vida","family":"Mashayekhi","sequence":"additional","affiliation":[{"name":"Utrecht University , , Padualaan 8 , ,","place":["Utrecht, The Netherlands, 3584 CH"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Pesce","sequence":"additional","affiliation":[{"name":"Wageningen University and Research , , ,","place":["Wageningen, The Netherlands, 6700 AA"]},{"name":"University of Zurich , , Winterthurerstrasse 190 , ,","place":["Zurich, Switzerland, 8057"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs J.","family":"van Haren","sequence":"additional","affiliation":[{"name":"Leiden University , , Sylviusweg 72 , ,","place":["Leiden, The Netherlands, 2333 BE"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-3006","authenticated-orcid":true,"given":"Nathaniel I.","family":"Martin","sequence":"additional","affiliation":[{"name":"Leiden University , , Sylviusweg 72 , ,","place":["Leiden, The Netherlands, 2333 BE"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"2026090123063421300_cit1","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1080\/10408398.2015.1077192","article-title":"Antimicrobial resistance:\nA global emerging threat to public health systems","volume":"57","author":"Ferri","year":"2017","journal-title":"Crit. 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