Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Bioorg Med Chem. 2011 Nov 15;19(22):6906-18. doi: 10.1016/j.bmc.2011.09.021. Epub 2011 Sep 17.

Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit.

Author information

  • 1Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.

Abstract

Based on modification of separate structural features of the Vibrio cholerae quorum sensing signal, (S)-3-hydroxytridecan-4-one (CAI-1), three focused compound libraries have been synthesized and evaluated for biological activity. Modifications to the acyl tail and α-hydroxy ketone typically provided agonists with activities correlated to tail length and conservative changes to the hydroxy ketone. Among the molecules identified within this collection of agonists is Am-CAI-1 (B11), which is among the most potent agonists reported to date with an EC(50) of 0.21 μM. Modifications to the ethyl side chain delivered molecules with both agonist and antagonist activity, including m-OH-Ph-CAI-1 (C13) which is the most potent antagonist reported to date with an IC(50) of 36 μM. The molecules described in this manuscript are anticipated to serve as valuable tools in the study of quorum sensing in Vibrio cholerae and provide new leads in the development of an antivirulence therapy against this human pathogen.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
22001326
[PubMed - indexed for MEDLINE]
PMCID:
PMC3673537
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Scheme 1
Scheme 2
Scheme 3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk