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Bioorg Med Chem. 2012 May 1;20(9):3128-42. doi: 10.1016/j.bmc.2012.01.048. Epub 2012 Feb 4.

Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure-activity study.

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1
Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.

Abstract

Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC(50) of 400 nM.

PMID:
22464688
PMCID:
PMC3753005
DOI:
10.1016/j.bmc.2012.01.048
[Indexed for MEDLINE]
Free PMC Article
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