Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors.
Journal
MedChemComm
ISSN: 2040-2511
Titre abrégé: Medchemcomm
Pays: England
ID NLM: 101531525
Informations de publication
Date de publication:
01 Apr 2019
01 Apr 2019
Historique:
received:
23
11
2018
accepted:
06
03
2019
pmc-release:
08
03
2020
entrez:
7
5
2019
pubmed:
7
5
2019
medline:
7
5
2019
Statut:
epublish
Résumé
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 chelator strength 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 peptides were 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 meropenem activity. However, evaluation of toxicity on different cancer cell lines demonstrated a similar trend, and thus inclusion of the bacterial peptides did possess rather high toxicity towards eukaryotic cells.
Identifiants
pubmed: 31057732
doi: 10.1039/c8md00578h
pii: c8md00578h
pmc: PMC6482411
doi:
Types de publication
Journal Article
Langues
eng
Pagination
528-537Références
Eur J Biochem. 1976 Sep 15;68(2):581-9
pubmed: 10161
J Am Chem Soc. 2003 Aug 13;125(32):9612-8
pubmed: 12904027
J Med Chem. 2004 Jul 29;47(16):3972-90
pubmed: 15267236
J Am Chem Soc. 2005 Jan 26;127(3):818-9
pubmed: 15656603
Biochemistry. 2005 Jun 14;44(23):8207-17
pubmed: 15938610
Org Lett. 2007 Nov 22;9(24):4999-5002
pubmed: 17956110
J Am Chem Soc. 2009 Oct 14;131(40):14345-54
pubmed: 19807181
Antimicrob Agents Chemother. 2010 Jan;54(1):346-52
pubmed: 19884381
Dalton Trans. 2009 Dec 7;(45):10044-54
pubmed: 19904432
Front Microbiol. 2013 Mar 14;4:48
pubmed: 23504089
Inorg Chem. 2013 May 20;52(10):5838-50
pubmed: 23621758
ACS Med Chem Lett. 2011 Jan 11;2(3):219-23
pubmed: 24900305
Nature. 2014 Jun 26;510(7506):503-6
pubmed: 24965651
Lancet. 2015 Jan 31;385(9966):430-40
pubmed: 25280870
Biochemistry. 2014 Oct 21;53(41):6530-8
pubmed: 25302576
Medchemcomm. 2016 Jan 1;7(1):141-147
pubmed: 26918106
Antimicrob Agents Chemother. 2016 Aug 22;60(9):5454-8
pubmed: 27381386
ACS Infect Dis. 2015 Nov 13;1(11):533-43
pubmed: 27623408
Medchemcomm. 2016 Sep 1;7(9):1694-1715
pubmed: 27642504
Drug Resist Updat. 2016 Nov;29:30-46
pubmed: 27912842
Future Med Chem. 2017 May;9(7):673-691
pubmed: 28504895
Genome Announc. 2017 Jul 6;5(27):
pubmed: 28684580
ACS Infect Dis. 2018 Feb 9;4(2):135-145
pubmed: 29091730
Bioorg Med Chem Lett. 2018 Jan 15;28(2):214-221
pubmed: 29248295
ACS Infect Dis. 2018 Sep 14;4(9):1407-1422
pubmed: 30022668
Biochemistry. 1976 Jul 13;15(14):3146-52
pubmed: 8084