Design, Synthesis and Biological Evaluation of N-Sulfonyl Homoserine Lactone Derivatives as Inhibitors of Quorum Sensing in Chromobacterium violaceum
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Results and Discussion
2.2.1. Antibacterial Activity
2.2.2. Quorum Sensing Inhibition
Compound | R | IC50(μM) |
---|---|---|
5a | (CH2)2CH3 | NA a |
5b | (CH2)3CH3 | 48.49 ± 2.68 |
5c | (CH2)4CH3 | 29.00 ± 2.41 |
5d | (CH2)5CH3 | NA a |
5e | 17.25 ± 2.60 | |
5f | 14.72 ± 2.58 | |
5g | 7.79 ± 2.68 | |
5h | 1.64 ± 0.27 | |
5i | 15.86 ± 2.35 | |
5j | 8.56 ± 1.25 | |
5k | 1.66 ± 0.33 | |
5l | 4.91 ± 0.97 | |
C10-HSL | 0.32 ± 0.07 |
2.2.3. Molecular Docking Studies
3. Experimental
3.1. General
3.2. Chemical Synthesis
3.2.1. Synthesis of Compounds 2–5
3.2.2. General Procedure for of the Preparation of Compounds 5–10
3.3. Evaluation of the Biological Activity
4. Conclusions
Supplementary Materials
Acknowledgments
References
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- Steven, A.M.; Queneau, Y.; Soulère, L.; von Bodman, S.; Doutheau, A. Mechanisms and Synthetic Modulators of AHL-Dependent Gene Regulation. Chem. Rev. 2011, 111, 4–27. [Google Scholar] [CrossRef]
- Churchill, M.E.; Chen, L. Structural Basis of Acyl-homoserine Lactone-Dependent Signaling. Chem. Rev. 2011, 111, 68–85. [Google Scholar] [CrossRef]
- Galloway, W.R.; Hodgkinson, J.T.; Bowden, S.D.; Welch, M.; Spring, D.R. Quorum Sensing in Gram Negative Bacteria: Small-Molecule Modulation of AHL and AI-2 Quorum Sensing Pathways. Chem. Rev. 2011, 111, 28–67. [Google Scholar] [CrossRef]
- Boukraa, M.; Sabbah, M.; Soulère, L.; EI Efrit, M.L.; Queneau, Y.; Doutheau, A. AHL-dependent quorum sensing inhibition: Synthesis and biological evaluation of α-(N-alkyl-carboxamide)-γ-butyrolactones andα-(N-alkyl-sulfonamide)-γ-butyrolactones. Bioorg. Med. Chem. Lett. 2011, 21, 6876–6879. [Google Scholar] [CrossRef]
- Geake, G.D.; Wezeman, R.J.; Siegel, A.P.; Blackwell, H.E. Small Molecule Inhibitors of Bacterial Quorum Sensing and Biofilm Formation. J. Am. Chem. Soc. 2005, 127, 12762–12763. [Google Scholar] [CrossRef]
- Reverchon, S.; Chanteqrel, B.; Deshayes, C.; Doutheau, A; Cotte-Pattat, N. New Synthetic Analogues of N-Acyl Homoserine Lactones as Agonists or Antagonists of Transcriptional Regulators Involved in Bacterial Quorum Sensing. Bioorg. Med. Chem. 2002, 12, 1153–1157. [Google Scholar] [CrossRef]
- Choo, J.H.; Rukayadi, Y.; Hwang, J.K. Inhibition of bacterial quorum sensing by vanilla extract. Lett. Appl. Microbiol. 2006, 42, 637–641. [Google Scholar]
- McClean, K.H.; Winson, M.K.; Fish, L.; Taylor, A.; Chhabra, S.R.; Camara, M.; Daykin, M.; Lamb, J.H.; Swift, S.; Bycroft, B.W.; et al. Quorum sensing and Chrornobacteriurn violaceurn: Exploitation of violacein production and inhibition for the detection of N-acyl homoserine lactones. Microbiology 1997, 143, 3703–3711. [Google Scholar] [CrossRef]
- Swem, L.R.; Swem, D.L.; O’Loughlin, C.T.; Gatmaitan, R.; Zhao, B.; Ulrich, S.M.; Basster, B.L. A Quorum-Sensing antagonist targets both membrane-bound and cytoplasmic receptors and controls bacterial pathogenicity. Mol. Cell 2009, 35, 143–153. [Google Scholar] [CrossRef]
- Chen, G.; Swem, L.R.; Swem, D.L.; O’Loughlin, C.T.; Jeffrey, P.D.; Bassler, B.L.; Hughson, F.M. A strategy for antagonizing quorum sensing. Mol. Cell 2011, 42, 199–209. [Google Scholar] [CrossRef]
- Fuqua, C.; Parsek, M.R.; Greenberg, E.P. Regulation of gene expression by cell-to-cell communication Acyl-homoserine lactone quorum sensing. Annu. Rev. Genet. 2001, 35, 439–468. [Google Scholar] [CrossRef]
- Choudhary, S.; Schmidt-Dannert, C. Application of quorum sensing in biotechnology. Appl. Microbiol. Biot. 2010, 86, 1267–1279. [Google Scholar] [CrossRef]
- Castang, S.; Chantegrel, B.; Deshayes, C.; Dolmazon, R.; Gouet, P.; Haser, R.; Reverchon, S.; Nasser, W.; Hugouvieux-Cotte-Pattat, N.; Doutheau, A. N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing. Bioorg. Med. Chem. Lett. 2004, 14, 5145–5149. [Google Scholar] [CrossRef]
- Brackman, G.; Risseeuw, M.; Celen, S.; Cos, P.; Maes, L.; Neils, H.J.; Calenbergh, S.V.; Coenye, T. Synthesis and evaluation of the quorum sensing inhibitory effect of substituted triazolyldihydrofuranones. Bioorg. Med. Chem. 2012, 20, 4737–4743. [Google Scholar] [CrossRef]
- Sabbah, M.; Fanny, F.; Grand, L.; Boukraa, M.; Efrit, M.L.; Doutheau, A.; Soulère, L.; Queneau, Y. Synthesis and biological evaluation of new N-acyl-homoserine-lactone analogues, base on triazole and tetrazole scaffolds, acting as LuxR-dependent quorum sensing modulators. Bioorg. Med. Chem. 2012, 20, 4727–4736. [Google Scholar] [CrossRef]
- Nielsen, J.; Givskov, M. Compounds and Methods for controlling bacterial virulence field of the invention. WO03/106445 A1, 24 December 2013. [Google Scholar]
- McLean, R.J.; Pierson, L.S.; Fuqua, C. A simple screening protocol for the identification of quorum signal antagonists. J. Microbiol. Methods. 2004, 58, 351–360. [Google Scholar] [CrossRef]
- Olivero, J.T.; Pájaro, N.P.; Stashenko, E. Antiquorum sensing activity of essential oils isolated from different species of the genus piper. Vitea revista de la facultad de quimica farmaceutica 2011, 18, 2145–2660. [Google Scholar]
- Sample Availability: Samples of the compounds 5a–l are available from the authors.
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Zhao, M.; Yu, Y.; Hua, Y.; Feng, F.; Tong, Y.; Yang, X.; Xiao, J.; Song, H. Design, Synthesis and Biological Evaluation of N-Sulfonyl Homoserine Lactone Derivatives as Inhibitors of Quorum Sensing in Chromobacterium violaceum. Molecules 2013, 18, 3266-3278. https://doi.org/10.3390/molecules18033266
Zhao M, Yu Y, Hua Y, Feng F, Tong Y, Yang X, Xiao J, Song H. Design, Synthesis and Biological Evaluation of N-Sulfonyl Homoserine Lactone Derivatives as Inhibitors of Quorum Sensing in Chromobacterium violaceum. Molecules. 2013; 18(3):3266-3278. https://doi.org/10.3390/molecules18033266
Chicago/Turabian StyleZhao, Mingming, Yingying Yu, Yuhui Hua, Fan Feng, Yigang Tong, Xiaohong Yang, Junhai Xiao, and Hongrui Song. 2013. "Design, Synthesis and Biological Evaluation of N-Sulfonyl Homoserine Lactone Derivatives as Inhibitors of Quorum Sensing in Chromobacterium violaceum" Molecules 18, no. 3: 3266-3278. https://doi.org/10.3390/molecules18033266