{"entity": "researcher", "timestamp": "2026-08-20T20:45:59.835Z", "family": "Shungube", "given": "Mbongeni", "initials": "M", "orcid": "0000-0001-8405-584X", "affiliations": ["Catalysis and Peptide Research Unit, University of KwaZulu Natal Durban 4001 South Africa naickert1@ukzn.ac.za +27 312601845."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d0b9cb57fef4ce5bb7d3c3b04b54f7e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d0b9cb57fef4ce5bb7d3c3b04b54f7e"}}, "publications": [{"entity": "publication", "iuid": "8614dee89659412aa9b3afb019db1a61", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8614dee89659412aa9b3afb019db1a61.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8614dee89659412aa9b3afb019db1a61"}}, "title": "Synthesis and biological evaluation of novel \u03b2-lactam-metallo \u03b2-lactamase inhibitors.", "authors": [{"family": "Shungube", "given": "Mbongeni", "initials": "M", "orcid": "0000-0001-8405-584X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d0b9cb57fef4ce5bb7d3c3b04b54f7e.json"}}, {"family": "Hlophe", "given": "Ayanda K", "initials": "AK"}, {"family": "Girdhari", "given": "Letisha", "initials": "L", "orcid": "0000-0001-5841-2735", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74d106eb83ef42fea7dc909edcde6337.json"}}, {"family": "Sabe", "given": "Victor T", "initials": "VT"}, {"family": "Peters", "given": "Byron B", "initials": "BB"}, {"family": "Reddy", "given": "Nakita", "initials": "N", "orcid": "0000-0003-4428-2241", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c720c72b0734659b2cc966792015076.json"}}, {"family": "Omolabi", "given": "Kehinde F", "initials": "KF"}, {"family": "Chetty", "given": "Lloyd", "initials": "L"}, {"family": "Arumugam", "given": "Thilona", "initials": "T"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3af870f9207f43e5ae3b802495214724.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88f669867879452ca86ab92c27fd285c.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84789ce64d004c83919336cdf43c903e.json"}}, {"family": "Qin", "given": "Hua-Li", "initials": "HL", "orcid": "0000-0002-6609-0083", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c7ffb7fb6d034b4a96adeb33b8564238.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5b1b1625e8c43859647736baa3e83d9.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T"}], "type": "journal article", "published": "2023-06-22", "journal": {"title": "RSC Adv.", "issn": "2046-2069", "volume": "13", "issue": "28", "pages": "18991-19001", "issn-l": "2046-2069"}, "abstract": "\u03b2-lactamases are enzymes that deactivate \u03b2-lactam antibiotics through a hydrolysis mechanism. There are two known types of \u03b2-lactamases: serine \u03b2-lactamases (SBLs) and metallo \u03b2-lactamases (MBLs). The two existing strategies to overcome \u03b2-lactamase-mediated resistance are (a) to develop novel \u03b2-lactam antibiotics that are not susceptible to hydrolysis by these enzymes; or (b) to develop \u03b2-lactamase inhibitors that deactivate the enzyme and thereby restore the efficacy of the co-administered antibiotics. Many commercially available SBL inhibitors are used in combination therapy with antibiotics to treat antimicrobial resistant infections; however, there are only a handful of MBL inhibitors undergoing clinical trials. In this study, we present 11 novel potential MBL inhibitors (via multi-step chemical synthesis), that have shown to completely restore the efficacy of meropenem (\u22642 mg L-1) against New Delhi metallo-\u03b2-lactamase (NDM) producing Klebsiella pneumoniae in vitro. These compounds contain a cyclic amino acid zinc chelator conjugated to various commercially available \u03b2-lactam antibiotic scaffolds with the aim to improve the overall drug transport, lipophilicity, and pharmacokinetic/pharmacodynamic properties as compared to the chelator alone. Biological evaluation of compounds 24b and 24c has further highlighted the downstream application of these MBLs, since they are non-toxic at the selected doses. Time-kill assays indicate that compounds 24b and 24c exhibit sterilizing activity towards NDM producing Klebsiella pneumoniae in vitro using minimal concentrations of meropenem. Furthermore, 24b and 24c proved to be promising inhibitors of VIM-2 (Ki = 0.85 and 1.87, respectively). This study has revealed a novel series of \u03b2-lactam MBLIs that are potent, efficacious, and safe leads with the potential to develop into therapeutic MBLIs.", "doi": "10.1039/d3ra02490c", "pmid": "37362332", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10285615"}, {"db": "pii", "key": "d3ra02490c"}], "notes": [], "created": "2026-08-20T09:27:44.094Z", "modified": "2026-08-20T09:27:44.324Z"}, {"entity": "publication", "iuid": "91a59cddd46c47eabc483341f2811cbf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/91a59cddd46c47eabc483341f2811cbf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/91a59cddd46c47eabc483341f2811cbf"}}, "title": "A 2018-2019 patent review of metallo beta-lactamase inhibitors.", "authors": [{"family": "Reddy", "given": "Nakita", "initials": "N", "orcid": "0000-0003-4428-2241", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c720c72b0734659b2cc966792015076.json"}}, {"family": "Shungube", "given": "Mbongeni", "initials": "M", "orcid": "0000-0001-8405-584X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d0b9cb57fef4ce5bb7d3c3b04b54f7e.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84789ce64d004c83919336cdf43c903e.json"}}, {"family": "Baijnath", "given": "Sooraj", "initials": "S", "orcid": "0000-0001-7860-1779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5cedc06c61074967821fce1c7dd757bb.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88f669867879452ca86ab92c27fd285c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77ef43839d9e476f95d124c9c34b81fa.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5b1b1625e8c43859647736baa3e83d9.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Expert Opin Ther Pat", "issn": "1744-7674", "volume": "30", "issue": "7", "pages": "541-555", "issn-l": null}, "abstract": "Antibiotic resistance caused by beta-lactamase expressing bacteria poses a concern given its global dissemination and proliferation. The emergence of the metallo beta-lactamases is an indefinite health threat toward which current antibiotics have limited clinical efficacy. One solution is to develop metallo beta-lactamase inhibitors (MBLIs) capable of restoring the activity of beta-lactam drugs.\n\nThis review focuses on potential metallo beta-lactamase inhibitors that have been patented during the period of 2018-2019. The aim is to provide insight into the diverse class of compounds which exhibit a synergistic inhibitory effect on carbapenem-resistant bacteria, when co-administered with a beta-lactam antibiotic.\n\nThe treatment strategy, of creating a broad-spectrum beta-lactamase inhibitor, is beneficial to the health sector as well as rural communities. Unfortunately, most of the inhibitors lack published data from both in vitro and in vivo evaluation, thus preventing an expert opinion on the likelihood to progress as candidates for clinical trials. From this report, the bismuth complexes, pyridinyl-nicotinamide derived sugars, boronic acid, and thiazole sulfonamide derivatives, portray promising properties for further advancement. Since there is currently no FDA approved MBLI, there remains an urgent need for the development of these combination treatment strategies.", "doi": "10.1080/13543776.2020.1767070", "pmid": "32393078", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:35:21.446Z", "modified": "2026-08-20T09:35:21.613Z"}]}