Metallo-β-lactamase inhibitor phosphonamidate monoesters
(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:
https://lup.lub.lu.se/record/9927831e-be70-475e-bb87-f22e739d9aa1
- author
- Palica, Katarzyna ; Vorácová, Manuela ; Skagseth, Susann ; Andersson Rasmussen, Anna LU ; Allander, Lisa ; Hubert, Madlen ; Sandgren, Linus ; Leiros, Hanna-Kirst ; Andersson, Hanna and Erdélyi, Máté
- organization
- publishing date
- 2022-01-25
- 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}}, }