Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors
| Autor: | Pal Rongved, Marc Le Borgne, Lars Petter Jordheim, Christopher Fröhlich, Sylvie Radix, Ove Alexander Høgmoen Åstrand, Anthony Prandina, Tor Gjøen, Silje Lauksund, Christian Schnaars, Ørjan Samuelsen, Adriana Magalhaes Santos Andresen, Geir Kildahl-Andersen |
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| Přispěvatelé: | Molécules bioactives et chimie médicinale (B2MC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, University Hospital of North Norway [Tromsø] (UNN), University of Oslo (UiO) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Stereochemistry
Pharmaceutical Science chemistry.chemical_element Ethylenediamine Peptide Zinc [CHIM.THER]Chemical Sciences/Medicinal Chemistry 01 natural sciences Biochemistry chemistry.chemical_compound [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication Drug Discovery Chelation Pharmacology chemistry.chemical_classification 010405 organic chemistry Organic Chemistry Affinities 0104 chemical sciences Chemistry 010404 medicinal & biomolecular chemistry Dipicolylamine chemistry Toxicity [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Molecular Medicine Peptidoglycan |
| Zdroj: | MedChemComm MedChemComm, Royal Society of Chemistry, In press, 10 (4), pp.528-537. ⟨10.1039/C8MD00578H⟩ |
| ISSN: | 2040-2503 2040-2511 |
| Popis: | International audience; The syntheses of metallo-β-lactamase inhibitors comprising chelating moieties, with varying zinc affinities,and peptides partly inspired from bacterial peptide sequences, have been undertaken. The zinc chelatorstrength was varied using the following chelators, arranged in order of ascending binding affinity:dipicolylamine (DPA, tridentate), dipicolyl-1,2,3-triazolylmethylamine (DPTA, tetradentate) dipicolyl ethylenediamine(DPED, tetradentate) and trispicolyl ethylenediamine (TPED, pentadentate). The chosen peptideswere mainly based on the known sequence of the C-terminus of the bacterial peptidoglycan precursors.Biological evaluation on clinical bacterial isolates, harbouring either the NDM-1 or VIM-2 metallo-β-lactamase, showed a clear relationship between the zinc chelator strength and restoration of meropenemactivity. However, evaluation of toxicity on different cancer cell lines demonstrated a similar trend, and thusinclusion of the bacterial peptides did possess rather high toxicity towards eukaryotic cells. |
| Databáze: | OpenAIRE |
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