ISSN:
1574-6968
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Biology
Notes:
IMP-1 metallo-β-lactamase is a zinc metalloenzyme that confers antibiotic resistance to bacteria through the hydrolysis of β-lactam antibiotics. Pathogens that express the enzyme show reduced susceptibility to carbapenems, such as meropenem and imipenem. In order to identify novel IMP-1 inhibitors, the National Cancer Institute (NCI) chemical diversity set was screened using 96-well high throughput screening format. The collection yielded several novel succinic acid derivatives that exhibited mixed inhibition of IMP-1 with compound 20707 having the highest affinity with a Ki value of 3.3 μM ± 1.7. The compounds are moderately potent inhibitors of IMP-1 with IC50 values ranging from 5.0 to 17 μM. An original chemical class of IMP-1 inhibitor, 2-((E)-(1,3-dihydroxy-2-methylpropan-2-ylimino)methyl)-4,6-diiodophenol, was discovered and was the most potent with an IC50 of 1.2 μM. NCI compounds, 20707, 140905 and 9746 sensitized a carbapenem-resistant laboratory strain of Escherichia coli to clinically achievable levels of meropenem.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1016/j.femsle.2004.11.042
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