{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:46:35Z","timestamp":1787319995036,"version":"build-2736575974"},"reference-count":24,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["PR1405\/7-1"],"award-info":[{"award-number":["PR1405\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Metallo beta lactamases (MBLs) are among the most problematic resistance mechanisms of multidrug-resistant Gram-negative pathogens due to their broad substrate spectrum and lack of approved inhibitors. In this study, we propose the integration of catechol substructures into the design of thiol-based MBL inhibitors, aiming at mimicking bacterial siderophores for the active uptake by the iron acquisition system of bacteria. We synthesised two catechol-containing MBL inhibitors, as well as their dimethoxy counterparts, and tested them for in vitro inhibitory activity against NDM-1, VIM-1, and IMP-7. We demonstrated that the most potent catechol-containing MBL inhibitor is able to bind Fe3+ ions. Finally, we could show that this compound restores the antibiotic activity of imipenem in NDM-1-expressing K. pneumoniae, while leaving HUVEC cells completely unaffected. Thus, siderophore-containing MBL inhibitors might be a valuable strategy to overcome bacterial MBL-mediated resistance to beta lactam antibiotics.<\/jats:p>","DOI":"10.3390\/molecules28041984","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:02:09Z","timestamp":1676858529000},"page":"1984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrating Siderophore Substructures in Thiol-Based Metallo-\u03b2-Lactamase Inhibitors"],"prefix":"10.3390","volume":"28","author":[{"given":"Marco J.","family":"Rotter","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Zentgraf","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Weizel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denia","family":"Frank","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Paul-Ehrlich-Stra\u00dfe 40, D-60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa D.","family":"Burgers","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Brunst","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9926-7578","authenticated-orcid":false,"given":"Robert","family":"F\u00fcrst","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Proschak","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Wichelhaus","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Paul-Ehrlich-Stra\u00dfe 40, D-60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewgenij","family":"Proschak","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Stra\u00dfe 9, D-60438 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"959107","DOI":"10.3389\/fmicb.2022.959107","article-title":"Drug Development Concerning Metallo-\u03b2-Lactamases in Gram-Negative Bacteria","volume":"13","author":"Li","year":"2022","journal-title":"Front. 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