Open Access
Journal of Medicinal Chemistry, volume 61, issue 3, pages 1255-1260
In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors
Cain Ricky L
1
,
Brem Jurgen
2
,
Zollman David
2
,
McDonough Michael
2
,
Johnson Rachel M.
1
,
Spencer James
3
,
Makena Anne
2
,
Abboud Martine I.
2
,
Cahill Samuel T
2
,
Lee Sook Y
2, 4
,
Mchugh Peter J
4
,
Schofield Christopher J.
2
,
WG Fishwick Colin
1
1
School
of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom
|
2
3
School
of Cellular and Molecular Medicine, University of Bristol, Biomedical
Sciences Building, Bristol BS8 1TD, United Kingdom
|
Publication type: Journal Article
Publication date: 2018-01-10
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
Zinc ion-dependent β-lactamases (MBLs) catalyze the hydrolysis of almost all β-lactam antibiotics and resist the action of clinically available β-lactamase inhibitors. We report how application of in silico fragment-based molecular design employing thiol-mediated metal anchorage leads to potent MBL inhibitors. The new inhibitors manifest potent inhibition of clinically important B1 subfamily MBLs, including the widespread NDM-1, IMP-1, and VIM-2 enzymes; with lower potency, some of them also inhibit clinically relevant Class A and D serine-β-lactamases. The inhibitors show selectivity for bacterial MBL enzymes compared to that for human MBL fold nucleases. Cocrystallization of one inhibitor, which shows potentiation of Meropenem activity against MBL-expressing Enterobacteriaceae, with VIM-2 reveals an unexpected binding mode, involving interactions with residues from conserved active site bordering loops.
Citations by journals
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3
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European Journal of Medicinal Chemistry
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3 publications, 8.11%
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1 publication, 2.7%
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Antibiotics
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1 publication, 2.7%
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Biomolecules
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Biomolecules
1 publication, 2.7%
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ACS Omega
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ACS Omega
1 publication, 2.7%
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International Journal of Molecular Sciences
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International Journal of Molecular Sciences
1 publication, 2.7%
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Frontiers in Microbiology
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Frontiers in Microbiology
1 publication, 2.7%
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Medicinal Chemistry Research
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Medicinal Chemistry Research
1 publication, 2.7%
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Nature Reviews Chemistry
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1 publication, 2.7%
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Microbiological Research
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Microbiological Research
1 publication, 2.7%
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Journal of Inorganic Biochemistry
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Journal of Inorganic Biochemistry
1 publication, 2.7%
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Trends in Pharmacological Sciences
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Trends in Pharmacological Sciences
1 publication, 2.7%
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Chemical Biology and Drug Design
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Chemical Biology and Drug Design
1 publication, 2.7%
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Medicinal Research Reviews
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Medicinal Research Reviews
1 publication, 2.7%
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ACS Catalysis
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1 publication, 2.7%
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MedChemComm
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MedChemComm
1 publication, 2.7%
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RSC Medicinal Chemistry
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RSC Medicinal Chemistry
1 publication, 2.7%
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FEMS Microbiology Reviews
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FEMS Microbiology Reviews
1 publication, 2.7%
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Journal of Biomolecular Structure and Dynamics
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1 publication, 2.7%
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Science advances
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1 publication, 2.7%
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Bioorganic and Medicinal Chemistry
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1 publication, 2.7%
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Journal of Enzyme Inhibition and Medicinal Chemistry
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Journal of Enzyme Inhibition and Medicinal Chemistry
1 publication, 2.7%
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1
2
3
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Citations by publishers
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1
2
3
4
5
6
7
8
9
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Elsevier
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Elsevier
9 publications, 24.32%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
8 publications, 21.62%
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Wiley
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Wiley
4 publications, 10.81%
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
3 publications, 8.11%
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Springer Nature
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Springer Nature
2 publications, 5.41%
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Royal Society of Chemistry (RSC)
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Royal Society of Chemistry (RSC)
2 publications, 5.41%
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Taylor & Francis
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Taylor & Francis
2 publications, 5.41%
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Bentham Science
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Bentham Science
1 publication, 2.7%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 2.7%
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Oxford University Press
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Oxford University Press
1 publication, 2.7%
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American Association for the Advancement of Science (AAAS)
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American Association for the Advancement of Science (AAAS)
1 publication, 2.7%
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1
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Cain R. L. et al. In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 3. pp. 1255-1260.
GOST all authors (up to 50)
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Cain R. L., Brem J., Zollman D., McDonough M., Johnson R. M., Spencer J., Makena A., Abboud M. I., Cahill S. T., Lee S. Y., Mchugh P. J., Schofield C. J., WG Fishwick C. In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors // Journal of Medicinal Chemistry. 2018. Vol. 61. No. 3. pp. 1255-1260.
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TY - JOUR
DO - 10.1021/acs.jmedchem.7b01728
UR - https://doi.org/10.1021%2Facs.jmedchem.7b01728
TI - In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors
T2 - Journal of Medicinal Chemistry
AU - Zollman, David
AU - Makena, Anne
AU - Lee, Sook Y
AU - Abboud, Martine I.
AU - Schofield, Christopher J.
AU - WG Fishwick, Colin
AU - Cain, Ricky L
AU - Brem, Jurgen
AU - McDonough, Michael
AU - Johnson, Rachel M.
AU - Spencer, James
AU - Cahill, Samuel T
AU - Mchugh, Peter J
PY - 2018
DA - 2018/01/10 00:00:00
PB - American Chemical Society (ACS)
SP - 1255-1260
IS - 3
VL - 61
SN - 0022-2623
SN - 1520-4804
ER -
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@article{2018_Cain,
author = {David Zollman and Anne Makena and Sook Y Lee and Martine I. Abboud and Christopher J. Schofield and Colin WG Fishwick and Ricky L Cain and Jurgen Brem and Michael McDonough and Rachel M. Johnson and James Spencer and Samuel T Cahill and Peter J Mchugh},
title = {In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors},
journal = {Journal of Medicinal Chemistry},
year = {2018},
volume = {61},
publisher = {American Chemical Society (ACS)},
month = {jan},
url = {https://doi.org/10.1021%2Facs.jmedchem.7b01728},
number = {3},
pages = {1255--1260},
doi = {10.1021/acs.jmedchem.7b01728}
}
Cite this
MLA
Copy
Cain, Ricky L., et al. “In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors.” Journal of Medicinal Chemistry, vol. 61, no. 3, Jan. 2018, pp. 1255-1260. https://doi.org/10.1021%2Facs.jmedchem.7b01728.