Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar 13;18(3):3266-78.
doi: 10.3390/molecules18033266.

Design, synthesis and biological evaluation of N-sulfonyl homoserine lactone derivatives as inhibitors of quorum sensing in Chromobacterium violaceum

Mingming Zhao  1 , Yingying Yu, Yuhui Hua, Fan Feng, Yigang Tong, Xiaohong Yang, Junhai Xiao, Hongrui Song
Affiliations

Design, synthesis and biological evaluation of N-sulfonyl homoserine lactone derivatives as inhibitors of quorum sensing in Chromobacterium violaceum

Mingming Zhao et al. Molecules. .

Abstract

A novel series of N-sulfonyl homoserine lactone derivatives 5a-l has been designed, synthesized and evaluated for quorum sensing inhibitory activities towards violacein production. Of the compounds synthesized, compound 5h was found to possess an excellent level of enantiopurity (99.2% e.e.). The results indicated that compounds bearing an ortho substituent on their phenyl ring exhibited excellent levels of inhibitory activity against violacein production. Compounds 5h and 5k in particular, with IC₅₀ values of 1.64 and 1.66 µM, respectively, were identified as promising lead compounds for further structural modification.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of C10-HSL, CL and target compounds 5a–l.
Scheme 1
Scheme 1
Synthesis of target compounds.
Figure 2
Figure 2
Antibacterial spot tests of compounds 5h,k.
Figure 3
Figure 3
Molecular model of CviR with C6-HSL and compound 5h bound to the active site.
See this image and copyright information in PMC

References

    1. Geske G.D., O’Nell J.C., Miller D.M., Mattmann M.E., Blackwell H.E. Modulation of Bacterial Quorum Sensing with Synthetic Ligands: Systematic Evaluation of N-Acylated Homoserine Lactones in Multiple Species and New Insights into Their Mechanisms of Action. J. Am. Chem. Soc. 2007;129:13613–13625. - PMC - PubMed
    1. Yang L., Liu Y., Stemberg C., Molin S. Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents. Molecules. 2010;15:780–792. doi: 10.3390/molecules15020780. - DOI - PMC - PubMed
    1. Amara N., Mashiach R., Amar D., Krief P., Spieser S.A.H., Bottomley M.J., Aharoni A., Meijler M.M. Covalent Inhibition of Bacterial Quorum Sensing. J. Am. Chem. Soc. 2009;131:10610–10619. doi: 10.1021/ja903292v. - DOI - PubMed
    1. Persson T., Hansen T.H., Rasmussen T.B., Skindersø M.E., Givskov M., Nielsen J. Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic. Org. Biomol. Chem. 2005;3:253–262. - PubMed
    1. Kim C., Kim J., Park H.Y., Park H.J., Kim C.K., Yoon J., Lee J.H. Development of Inhibitors against TraR Quorum-Sensing System in Agrobacterium tumefaciens by Molecular Modeling of the Ligand-Receptor Interaction. Mol. Cells. 2009;28:447–453. doi: 10.1007/s10059-009-0144-6. - DOI - PubMed

Publication types

MeSH terms