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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa
Chemical Biology and Drug Design, Volume 80, No. 4, Year 2012
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Description
Metallo-β-lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β-lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine-2-thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP-1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested (1a, 3b, 5c, 6b, 7a, 8a, 11c, 13a, and 16a) showed micromolar inhibition constants (Ki values range from ~20-80μm). Compounds 1c, 2b, and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (Ki=19±9μm), as well as 7a (Ki=21±10μm), the strongest inhibitor of the pyrrole series, in the active site of IMP-1. © 2012 John Wiley & Sons A/S.
Authors & Co-Authors
Hussein, Waleed M.
Egypt, Helwan
Faculty of Pharmacy
Australia, Brisbane
The University of Queensland
Fatahala, Samar S.
Egypt, Helwan
Faculty of Pharmacy
Khoder, Zainab M.
Egypt, Helwan
Faculty of Pharmacy
McGeary, Ross P.
Australia, Brisbane
The University of Queensland
Schenk, Gerhard
Australia, Brisbane
The University of Queensland
Ireland, Maynooth
Maynooth University
Ollis, David L.
Australia, Canberra
The Australian National University
Mohamed, M. S.
Egypt, Helwan
Faculty of Pharmacy
Statistics
Citations: 53
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1111/j.1747-0285.2012.01440.x
ISSN:
17470277
e-ISSN:
17470285