Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Metallo-β-lactamase inhibitor phosphonamidate monoesters

Palica, Katarzyna ; Vorácová, Manuela ; Skagseth, Susann ; Andersson Rasmussen, Anna LU ; Allander, Lisa ; Hubert, Madlen ; Sandgren, Linus ; Leiros, Hanna-Kirst ; Andersson, Hanna and Erdélyi, Máté (2022) In ACS Omega 7(5). p.4550-4562
Abstract
Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic... (More)
Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-β-lactamase-resistant bacteria. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Omega
volume
7
issue
5
pages
4550 - 4562
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:35155946
  • scopus:85124146868
ISSN
2470-1343
DOI
10.1021/acsomega.1c06527
language
English
LU publication?
yes
id
9927831e-be70-475e-bb87-f22e739d9aa1
date added to LUP
2023-10-10 16:37:48
date last changed
2023-10-17 15:33:11
@article{9927831e-be70-475e-bb87-f22e739d9aa1,
  abstract     = {{Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-β-lactamase-resistant bacteria.}},
  author       = {{Palica, Katarzyna and Vorácová, Manuela and Skagseth, Susann and Andersson Rasmussen, Anna and Allander, Lisa and Hubert, Madlen and Sandgren, Linus and Leiros, Hanna-Kirst and Andersson, Hanna and Erdélyi, Máté}},
  issn         = {{2470-1343}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{5}},
  pages        = {{4550--4562}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Omega}},
  title        = {{Metallo-β-lactamase inhibitor phosphonamidate monoesters}},
  url          = {{http://dx.doi.org/10.1021/acsomega.1c06527}},
  doi          = {{10.1021/acsomega.1c06527}},
  volume       = {{7}},
  year         = {{2022}},
}