Inhibition of metallo-β-lactamases by a series of thiol ester derivatives of mercaptophenylacetic acid

Abstract A series of mercaptophenylacetic acid thiol esters bearing a phenyl substituent adjacent to the carboxylic acid function has been shown to be inhibitors of metallo-β-lactamases. The inhibition of the Bacteroides fragilis CfiA and Bacillus cereus II metallo-β-lactamases was Zn2+ dependent, g...

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Bibliographic Details
Published in:FEMS microbiology letters 1997-12, Vol.157 (1), p.171-175
Main Authors: Payne, David J., Bateson, John H., Gasson, Brian C., Khushi, Teresa, Proctor, David, Pearson, Stewart C., Reid, Robert
Format: Article
Language:English
Subjects:
Calorimetry
Carboxylic acids
Chelation
Esters
Inhibition
Inhibitors
Mercaptophenylacetic acid
Metallo-β-lactamase
Metalloenzyme
Metallography
Microbiology
Thioesters
Thiolester
Titration
Titration calorimetry
Zinc
Zinc sulfate
β‐Lactamase
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Summary:Abstract A series of mercaptophenylacetic acid thiol esters bearing a phenyl substituent adjacent to the carboxylic acid function has been shown to be inhibitors of metallo-β-lactamases. The inhibition of the Bacteroides fragilis CfiA and Bacillus cereus II metallo-β-lactamases was Zn2+ dependent, greater inhibition being observed at 1 μM ZnSO4 than at 100 μM ZnSO4. Despite this Zn2+ dependency, isothermal titration calorimetry studies illustrated that representative compounds had no detectable affinity for Zn2+ (K>1 mM). This indicates that their mode of inhibition was not by chelation of the active site Zn2+. Greatest potency was observed against the Stenotrophomonas maltophilia L1 metallo-β-lactamase with I50 values of between
ISSN:0378-1097
1574-6968
DOI:10.1111/j.1574-6968.1997.tb12769.x