{"entity": "researcher", "timestamp": "2026-07-17T08:59:28.834Z", "family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "affiliations": ["Catalysis and Peptide Research Unit", "University of KwaZulu Natal", "Durban", "South Africa"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c"}}, "publications": [{"entity": "publication", "iuid": "f8b2aad10ba84e868680d663819912c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8b2aad10ba84e868680d663819912c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8b2aad10ba84e868680d663819912c7"}}, "title": "Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel \u03b2-Lactam-Metallo-\u03b2-Lactamase Inhibitors.", "authors": [{"family": "Reddy", "given": "Nakita", "initials": "N"}, {"family": "Girdhari", "given": "Letisha", "initials": "L", "orcid": "0000-0001-5841-2735", "researcher": {"href": "https://publications.scilifelab.se/researcher/249183863e6842a59f3b2bba5c3d0670.json"}}, {"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Gouws", "given": "Arnoldus C", "initials": "AC", "orcid": "0000-0002-9848-719X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba06527dc4bd4d54b7ccf4db223f0691.json"}}, {"family": "Peters", "given": "Byron K", "initials": "BK"}, {"family": "Rajbongshi", "given": "Kamal K", "initials": "KK", "orcid": "0000-0003-0128-663X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b42da27a8b384a6684037107d0a158ca.json"}}, {"family": "Baijnath", "given": "Sooraj", "initials": "S", "orcid": "0000-0001-7860-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/a918cd14121f40bf88ad33082921e5c2.json"}}, {"family": "Mdanda", "given": "Sipho", "initials": "S", "orcid": "0000-0003-0146-0538", "researcher": {"href": "https://publications.scilifelab.se/researcher/564e56b376b04f2d996a425c16013a77.json"}}, {"family": "Ntombela", "given": "Thandokuhle", "initials": "T"}, {"family": "Arumugam", "given": "Thilona", "initials": "T"}, {"family": "Bester", "given": "Linda A", "initials": "LA", "orcid": "0000-0001-5726-681X", "researcher": {"href": "https://publications.scilifelab.se/researcher/15b4bc949845434a9b612be0e28764a5.json"}}, {"family": "Singh", "given": "Sanil D", "initials": "SD"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications.scilifelab.se/researcher/f96bfd695ee44484ad9b87f9ef4e76a0.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}], "type": "journal article", "published": "2023-03-23", "journal": {"title": "Antibiotics (Basel)", "issn": "2079-6382", "issn-l": null, "volume": "12", "issue": "4", "pages": null}, "abstract": "Virulent Enterobacterale strains expressing serine and metallo-\u03b2-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop \u03b2-lactamase inhibitors to counter this resistance. Currently, serine \u03b2-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-\u03b2-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived \u03b2-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of \u22641 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 \u00b5M and 30.9 \u00b5M against New Delhi Metallo-\u03b2-lactamase (NDM-1) and Verona Integron-encoded Metallo-\u03b2-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 \u00b5M, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).", "doi": "10.3390/antibiotics12040633", "pmid": "37106995", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10135050"}, {"db": "pii", "key": "antibiotics12040633"}], "notes": [], "created": "2024-01-16T15:19:03.368Z", "modified": "2025-10-17T13:05:07.644Z"}, {"entity": "publication", "iuid": "c0c0048885944b84a524ece147e977f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0c0048885944b84a524ece147e977f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0c0048885944b84a524ece147e977f4"}}, "title": "In Vitro and In Vivo Development of a \u03b2-Lactam-Metallo-\u03b2-Lactamase Inhibitor: Targeting Carbapenem-Resistant Enterobacterales.", "authors": [{"family": "Peters", "given": "Byron K", "initials": "BK", "orcid": "0000-0003-2889-1354", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbb194a36bfa4a8ca6203ddc5063d033.json"}}, {"family": "Reddy", "given": "Nakita", "initials": "N"}, {"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Girdhari", "given": "Letisha", "initials": "L"}, {"family": "Baijnath", "given": "Sooraj", "initials": "S"}, {"family": "Mdanda", "given": "Sipho", "initials": "S"}, {"family": "Chetty", "given": "Lloyd", "initials": "L"}, {"family": "Ntombela", "given": "Thandokuhle", "initials": "T"}, {"family": "Arumugam", "given": "Thilona", "initials": "T"}, {"family": "Bester", "given": "Linda A", "initials": "LA"}, {"family": "Singh", "given": "Sanil D", "initials": "SD"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications.scilifelab.se/researcher/f96bfd695ee44484ad9b87f9ef4e76a0.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI"}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}], "type": "journal article", "published": "2023-03-10", "journal": {"title": "ACS Infect Dis", "issn": "2373-8227", "issn-l": null, "volume": "9", "issue": "3", "pages": "486-496"}, "abstract": "\u03b2-lactams are the most prescribed class of antibiotics due to their potent, broad-spectrum antimicrobial activities. However, alarming rates of antimicrobial resistance now threaten the clinical relevance of these drugs, especially for the carbapenem-resistant Enterobacterales expressing metallo-\u03b2-lactamases (MBLs). Antimicrobial agents that specifically target these enzymes to restore the efficacy of last resort \u03b2-lactam drugs, that is, carbapenems, are therefore desperately needed. Herein, we present a cyclic zinc chelator covalently attached to a \u03b2-lactam scaffold (cephalosporin), that is, BP1. Observations from in vitro assays (with seven MBL expressing bacteria from different geographies) have indicated that BP1 restored the efficacy of meropenem to \u2264 0.5 mg/L, with sterilizing activity occurring from 8 h postinoculation. Furthermore, BP1 was nontoxic against human hepatocarcinoma cells (IC50 > 1000 mg/L) and exhibited a potency of (K) 24.8 and 97.4 \u03bcM against Verona integron-encoded MBL (VIM-2) and New Delhi metallo \u03b2-lactamase (NDM-1), respectively. There was no inhibition observed from BP1 with the human zinc-containing enzyme glyoxylase II up to 500 \u03bcM. Preliminary molecular docking of BP1 with NDM-1 and VIM-2 sheds light on BP1's mode of action. In iappKlebsiella pneumoniae NDM infected mice, BP1 coadministered with meropenem was efficacious in reducing the bacterial load by >3 log10 units' postinfection. The findings herein propose a favorable therapeutic combination strategy that restores the activity of the carbapenem antibiotic class and complements the few MBL inhibitors under development, with the ultimate goal of curbing antimicrobial resistance.", "doi": "10.1021/acsinfecdis.2c00485", "pmid": "36786013", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10012271"}], "notes": [], "created": "2023-05-15T15:31:08.266Z", "modified": "2025-10-17T13:05:07.655Z"}, {"entity": "publication", "iuid": "c729c24ddb734e7a8fcdc83f567b8d8c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c729c24ddb734e7a8fcdc83f567b8d8c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c729c24ddb734e7a8fcdc83f567b8d8c"}}, "title": "Organic Base-Mediated Carboxylation of (Hetero)aromatic Compounds Using Supercritical Carbon Dioxide (scCO2)", "authors": [{"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}, {"family": "Chetty", "given": "Lloyd C", "initials": "LC", "orcid": "0000-0002-7343-9781", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2211fe9922447608a98c4208a4ac953.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}], "type": "journal-article", "published": "2022-11-00", "journal": {"title": "Synthesis", "issn": "0039-7881", "issn-l": null, "volume": "54", "issue": "21", "pages": "4827-4833"}, "abstract": null, "doi": "10.1055/a-1894-9073", "pmid": null, "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-12-05T09:45:33.151Z", "modified": "2025-10-17T13:05:07.734Z"}, {"entity": "publication", "iuid": "2eac4ffbee0246659c80bf49f67a8bd6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2eac4ffbee0246659c80bf49f67a8bd6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2eac4ffbee0246659c80bf49f67a8bd6"}}, "title": "Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction", "authors": [{"family": "Khumalo", "given": "Mzilikazi F", "initials": "MF"}, {"family": "Akpan", "given": "Ekemini D", "initials": "ED", "orcid": "0000-0003-2402-3402", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74fd4a40ee04edba2464ffbc2ed2e12.json"}}, {"family": "Chinthakindi", "given": "Praveen K", "initials": "PK", "orcid": "0000-0002-8344-2415", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5a011c248024881825b8f8c90df7237.json"}}, {"family": "Brasil", "given": "Edikarlos M", "initials": "EM", "orcid": "0000-0002-8837-2428", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2ef0786b73541ef933d4d09ffe9c0e0.json"}}, {"family": "Rajbongshi", "given": "Kamal K", "initials": "KK", "orcid": "0000-0003-0128-663X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b42da27a8b384a6684037107d0a158ca.json"}}, {"family": "Makatini", "given": "Maya M", "initials": "MM"}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}], "type": "journal-article", "published": "2018-00-00", "journal": {"volume": "8", "issn": "2046-2069", "issue": "65", "pages": "37503-37507", "title": "RSC Adv.", "issn-l": "2046-2069"}, "abstract": null, "doi": "10.1039/c8ra07627h", "pmid": null, "labels": {"Drug Discovery and Development": "Technology development"}, "xrefs": [], "notes": [], "created": "2019-01-10T09:50:56.016Z", "modified": "2025-10-17T13:05:08.577Z"}, {"entity": "publication", "iuid": "cf9baa521f3d4088831c3166439ae6f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf9baa521f3d4088831c3166439ae6f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf9baa521f3d4088831c3166439ae6f5"}}, "title": "An unexpected re-arrangement of the antibiotic carbapenem core to new 1,4-diazepin-5-one scaffolds", "authors": [{"family": "Peters", "given": "Byron K", "initials": "BK"}, {"family": "Razuwika", "given": "Rufaro", "initials": "R"}, {"family": "Samipillai", "given": "Marivel", "initials": "M"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T"}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}], "type": "journal-article", "published": "2018-00-00", "journal": {"volume": "8", "issn": "2046-2069", "issue": "1", "pages": "190-193", "title": "RSC Adv.", "issn-l": "2046-2069"}, "abstract": null, "doi": "10.1039/c7ra12688c", "pmid": null, "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2018-10-15T11:28:22.009Z", "modified": "2025-10-17T13:05:08.594Z"}, {"entity": "publication", "iuid": "b5010f5123d048bb97df84f0dcd57056", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5010f5123d048bb97df84f0dcd57056.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5010f5123d048bb97df84f0dcd57056"}}, "title": "Organocatalytic Mannich Reactions on a Carbapenem Core - Synthesis of Mannich Bases and Bicyclic Diazanonanes", "authors": [{"family": "Cele", "given": "Zamani E D", "initials": "ZED"}, {"family": "Pawar", "given": "Sachin A", "initials": "SA"}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}], "type": "journal-article", "published": "2014-04-00", "journal": {"volume": "2014", "issn": "1434-193X", "issue": "11", "pages": "2253-2260", "title": "Eur. J. Org. Chem.", "issn-l": "1099-0690"}, "abstract": null, "doi": "10.1002/ejoc.201301823", "pmid": null, "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-10-31T08:33:00.557Z", "modified": "2025-10-23T08:55:56.064Z"}, {"entity": "publication", "iuid": "b16949a1ad9f4a00b88070c367c39940", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b16949a1ad9f4a00b88070c367c39940.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b16949a1ad9f4a00b88070c367c39940"}}, "title": "Proline N-oxides: modulators of the 3D conformation of linear peptides through \u201cNO-turns\u201d", "authors": [{"family": "Farahani", "given": "Majid D", "initials": "MD"}, {"family": "Honarparvar", "given": "Bahareh", "initials": "B"}, {"family": "Albericio", "given": "Fernando", "initials": "F"}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}], "type": "journal-article", "published": "2014-00-00", "journal": {"volume": "12", "issn": "1477-0539", "issue": "25", "pages": "4479", "title": "Org. Biomol. Chem.", "issn-l": "1477-0520"}, "abstract": null, "doi": "10.1039/c4ob00433g", "pmid": "24849849", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-10-31T08:33:00.094Z", "modified": "2025-10-23T08:55:47.934Z"}]}