{"entity": "researcher", "timestamp": "2026-08-20T21:04:57.346Z", "family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "affiliations": ["School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal Durban South Africa."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/3af870f9207f43e5ae3b802495214724.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/3af870f9207f43e5ae3b802495214724"}}, "publications": [{"entity": "publication", "iuid": "5ee73cdf9e7c4df0b2f1e52549cff3a8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ee73cdf9e7c4df0b2f1e52549cff3a8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ee73cdf9e7c4df0b2f1e52549cff3a8"}}, "title": "Development and in vitro evaluation of 1,4,7-triazacyclononane-coupled \u03b2-lactams against metallo-\u03b2-lactamase producing bacteria.", "authors": [{"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Reddy", "given": "Nakita", "initials": "N", "orcid": "0000-0003-4428-2241", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c720c72b0734659b2cc966792015076.json"}}, {"family": "Ghazi", "given": "Terisha", "initials": "T"}, {"family": "Govender", "given": "Kimberleigh B", "initials": "KB", "orcid": "0000-0003-2372-5365", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac4af1fdc8014145b709012f09fad215.json"}}, {"family": "Singh", "given": "Ravesh", "initials": "R"}, {"family": "Kajee", "given": "Afsana", "initials": "A"}, {"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": "Tiwari", "given": "Dileep", "initials": "D"}, {"family": "Govender", "given": "Thavendran", "initials": "T"}, {"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": "2025-07-04", "journal": {"title": "RSC Adv.", "issn": "2046-2069", "volume": "15", "issue": "29", "pages": "23427-23440", "issn-l": "2046-2069"}, "abstract": "Antimicrobial resistance (AMR) is a critical global issue, particularly against \u03b2-lactam antibiotics, which comprise over 60% of prescriptions. Metallo-\u03b2-lactamases (MBLs) are especially concerning as they inactivate nearly all \u03b2-lactams, except monobactams. Unlike serine-\u03b2-lactamases (SBLs), for which inhibitors exist, there are no clinically approved MBL inhibitors; only taniborbactam is in pre-registration. This study introduces eight new MBL inhibitors (13a-f, 14a-b), designed using a 1,4,7-triazacyclononane (NO3PY) chelator linked to a \u03b2-lactam. These inhibitors restored the efficacy of meropenem, reducing its minimum inhibitory concentration (MIC) against MBL-expressing pathogens to <2 mg L-1. Time-kill assays confirmed bactericidal activity, with this series being non-toxic and highly specific, these compounds hold promising potential as MBL inhibitors.", "doi": "10.1039/d5ra01842k", "pmid": "40626067", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12230942"}, {"db": "pii", "key": "d5ra01842k"}], "notes": [], "created": "2026-08-20T09:28:15.994Z", "modified": "2026-08-20T09:28:16.135Z"}, {"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"}]}