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dc.contributor.authorPrandina, Anthony
dc.contributor.authorRadix, Sylvie
dc.contributor.authorLe Borgne, Marc
dc.contributor.authorJordheim, Lars Petter
dc.contributor.authorBousfiha, Zineb
dc.contributor.authorFröhlich, Christopher
dc.contributor.authorLeiros, Hanna-Kirsti S.
dc.contributor.authorSamuelsen, Ørjan
dc.contributor.authorFrøvold, Espen
dc.contributor.authorRongved, Pål
dc.contributor.authorÅstrand, Ove Alexander Høgmoen
dc.date.accessioned2020-03-27T08:13:35Z
dc.date.available2020-03-27T08:13:35Z
dc.date.issued2019-02-02
dc.description.abstractAntibiotics are key drugs in modern healthcare, especially in hospitals, where multiresistant bacteria resides and is a potential threat to human health. In the present work, a new series of adjuvants working synergistically with the carbapenem meropenem, in which a selective zinc-chelating agent was covalently linked to the small bacterial peptide D-Ala-D-Ala, was synthesized and tested against VIM-2 and NDM-1 metallo-β-lactamases (MBLs). The nature of the linker was modified in a structure-activity relationship study. Compound 1i, having an ethyl piperidine linker, lowered the MIC of meropenem from 32 to 64 mg/L to 2 and 1–2 mg/L against VIM-2- and NDM-1-producing clinical isolates, respectively. The IC50 value of 1i against VIM-2 was 9.8 and 2.2 μM after 5 and 20 min, respectively. Compound 1i also showed intrinsic toxicity against three eukaryotic human tumoral cell lines between 50 and 120 μM.en_US
dc.identifier.citationPrandina, A.; Radix, S.; Le Borgne, M.; Jordheim, L.P.; Bousfiha, Z,; Fröhlich, C.F.; Leiros, H.; Samuelsen, Ø.; Frøvold, E.; Rongved, P.R.; Åstrand, O.A.H. (2019) Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors. <i>Tetrahedron, 75,</i> (11), 1525-1540en_US
dc.identifier.cristinIDFRIDAID 1688051
dc.identifier.doi10.1016/j.tet.2019.02.004
dc.identifier.issn0040-4020
dc.identifier.issn1464-5416
dc.identifier.urihttps://hdl.handle.net/10037/17889
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalTetrahedron
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 Elsevier Ltd. All rights reserveden_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titleSynthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitorsen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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