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Arzneimittelforschung 2012; 62(07): 330-334
DOI: 10.1055/s-0032-1312590
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Biological Activities of Some 1,3-Benzoxazol-2(3H)-One Derivatives as Anti-Quorum Sensing Agents

A. M. Miandji
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey
,
S. Ulusoy
2   Department of Biology, Faculty of Arts and Sciences, Suleyman Demirel University, Isparta, Turkey
,
Y. Dündar
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey
,
S. Özgen
3   Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
,
F. K. Onurdağ
3   Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
,
G. Boşgelmez-Tınaz
2   Department of Biology, Faculty of Arts and Sciences, Suleyman Demirel University, Isparta, Turkey
4   Department of Clinical Microbiology, Faculty of Medicine, Marmara University, İstanbul, Turkey
,
N. Noyanalpan
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

received 27 March 2012

accepted 16 April 2012

Publication Date:
15 May 2012 (online)

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Synthesis and Biological Activities of Some 1,3-Benzoxazol-2(3H)-One Derivatives as Anti-Quorum Sensing AgentsArzneimittelforschung 2012; 62(07): e2-e2
DOI: 10.1055/s-0032-1315825

Abstract

Antibiotics are commonly used to treat microbial infections. Due to misuse or large-scale use of antibiotics, many pathogens have gained resistance which makes antibiotic treatments ineffective. The discovery that many bacteria use quorum sensing (QS) to regulate their virulence factor and pathogenicity production makes the QS system an attractive target for antimicrobial therapy. A series of 1,3-benzoxazol-2(3H)-one derivatives were designed and synthesized as QS inhibitors (QSIs) and tested for their QS inhibitory activities. In vitro quorum sensing inhibitor screen (QSIS) assay indicated that the 1,3-benzoxazol-2(3H)-one (compound 1), 5-chloro-1,3-benzoxazol-2(3H)-one (compound 6), 6-methyl-1,3-benzoxazol-2(3H)-one (compound 11), and 5-methyl-1,3-benzoxazol-2(3H)-one (compound 16), inhibit QS system in quorum sensing selector (QSIS)1 strain. These 4 QSIs also significantly reduced elastase production, biofilm formation and swarming motility of Pseudomonas aeruginosa PA01 strain. These results suggest that compound 1, 6, 11 and 16 may provide a starting point for the design and development of new anti-pathogenic drugs that restrict virulence of P. aeruginosa and possibly other clinically important human pathogens. In addition, these QSI molecules could potentially be used in combination with conventional antibiotics to increase the efficiency of disease control and to extend the life span of established antimicrobials.

Supporting information available online at http://www.thieme-connect.de/ejournals/toc/amf

Key words

acyl homoserine lactone - quorum sensing inhibitors - 1,3-benzoxazol-2(3H)-one

Supporting information

 

  • References

  • 1 Fuqua WC, Winans SC, Greenberg EP. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994; 176: 269-275
    PubMedSearch in Google Scholar
  • 2 Bassler BL, Losick R. Bacterially speaking. Cell 2006; 125: 237-246
    CrossrefPubMedSearch in Google Scholar
  • 3 Fugua C, Parsek MR, Greenberg EP. Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu Rev Genet 2001; 35: 439-468
    CrossrefPubMedSearch in Google Scholar
  • 4 Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol 2001; 55: 165-199
    CrossrefPubMedSearch in Google Scholar
  • 5 Pollack M. Pseudomonas aeruginosa. In: Mendel GL, Douglas RG, Bennet JE. (eds.). Principles and practice of infectious disease. New York: Churchill Livingstone; 1990. P 1673-1691
    Search in Google Scholar
  • 6 Govan JR, Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 1996; 60: 539-574
    PubMedSearch in Google Scholar
  • 7 Smith RS, Harris SG, Phillips R et al. The Pseudomonas aeruginosa quorum- sensing molecule N-(3-oxododeconoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 2002; 184: 1132-1139
    CrossrefPubMedSearch in Google Scholar
  • 8 Nicas TI, Iglewski BH. The contribution of exoproducts to virulence of Pseudomonas aeruginosa . Can J Microbiol 1985; 31: 387-392
    CrossrefPubMedSearch in Google Scholar
  • 9 van Delden C, Iglewski BH. Cell-to-cell signaling and Pseudomonas aeruginosa infections. Emerging Infect Dis 1998; 4: 551-560
    CrossrefPubMedSearch in Google Scholar
  • 10 Gambello MJ, Iglewski BH. Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression. J Bacteriol 1991; 173: 3000-3009
    PubMedSearch in Google Scholar
  • 11 Latifi A, Winson MK, Foglino M et al. Multiple homologs of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PA01. Mol Microbiol 1995; 17: 333-343
    CrossrefPubMedSearch in Google Scholar
  • 12 Williams P, Camara M. Quorum sensing and environmental adaptation in Pseudomonas aeruginosa: a tale of regulatory networks and multifunctional signal molecules. Curr Opin Microbiol 2009; 12: 182-191
    CrossrefPubMedSearch in Google Scholar
  • 13 Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science 1999; 284: 1318-1322
    CrossrefPubMedSearch in Google Scholar
  • 14 Raffa RB, Iannuzzo JR, Levine DR et al. Bacterial communication (“quorum sensing”) via ligands and receptors: A novel pharmacologic target for the design of antibiotic drugs. J Pharmacol Exp Ther 2005; 312: 417-423
    PubMedSearch in Google Scholar
  • 15 Estrela AB, Heck MG, Abraham WR. Novel approaches to control biofilm infections. Curr Med Chem 2009; 16: 1512-1530
    CrossrefPubMedSearch in Google Scholar
  • 16 Kociolek MG. Quorum sensing inhibitors and biofilms. Anti-infect Agents Med Chem 2009; 8: 315-326
    PubMedSearch in Google Scholar
  • 17 Høiby N, Bjarnsholt T, Givskov M et al. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Ag 2010; 35: 322-332
    CrossrefPubMedSearch in Google Scholar
  • 18 Antunes LCM, Ferreira RBR, Buckner MMC et al. Quorum sensing in bacterial virulence. Microbiology 2010; 156: 2271-2282
    CrossrefPubMedSearch in Google Scholar
  • 19 Galloway WRJD, Hodgkinson JT, Bowden SD et al. Quorum sensing in gram-negative bacteria: Small molecule modulation of AHL and AI-2 quorum sensing pathways. Chem Rev 2011; 111: 28-67
    CrossrefPubMedSearch in Google Scholar
  • 20 Yang L, Rybtke MT, Jakobsen TH et al. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. Antimicrob Agents Chemother 2009; 53: 2432-2443
    CrossrefPubMedSearch in Google Scholar
  • 21 Cankara Ş. Synthesis of some 6-(thiazole-4-il)-2-oxo-3H-benzoxazline derivatives and studies of their inhibitor effects on cyclooxygenase. MSc Thesis. Advisor Prof Dr Serdar Ünlü, 2007
    PubMedSearch in Google Scholar
  • 22 Bretschneider H, Piekarski G. Oxazoles and oxazolines. II. Synthesis of the ethyl ester of 2-dichloromethyl-2-oxazoline-4-carboxylic acid from the ethyl ester of serine and dichloroacetimino thio-ethyl ether. Monatsh Chem 1954; 85: 1110-1118
    CrossrefPubMedSearch in Google Scholar
  • 23 Gökhan N, Köksal M, Küpeli E et al. Some new Mannich bases of 5-methyl-2-benzoxazolinones with analgesis and anti-inflammatory activities. Turk J Chem 2005; 29: 445-454
    PubMedSearch in Google Scholar
  • 24 Zygmunt E. Investigation of hydroxamic acids. V. Lossen rearrangement of O-hydroxyarylhydroxamic acids. Roczniki Chemii 1954; 28: 549-560
    PubMedSearch in Google Scholar
  • 25 Doğruer DS, Ünlü S, Şahin MF et al. Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolon-3-yl- and 2-benzothiazolon-3-yl) acetic acid derivatives. Il Farmaco 1998; 53: 80-84
    CrossrefPubMedSearch in Google Scholar
  • 26 Cotelle N, Cotelle P, Lesieur D. Acylation of 2,3-dihydrobenzoxazol-2-one in a two-step method involving an acyl migration. Synthetic Commun 1989; 19: 3259-3266
    CrossrefPubMedSearch in Google Scholar
  • 27 Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS), Performance Standards for Antimicrobial Susceptibility Testing 16th Informational Supplement. CLSI M100-S18, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA, 2008
    PubMed
  • 28 Rasmussen TB, Bjarnsholt T, Skindersoe ME et al. Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 2005; 187: 1799-1814
    CrossrefPubMedSearch in Google Scholar
  • 29 Zhu H, Bandara R, Conibear TCR et al. Pseudomonas aeruginosa with LasI quorum-sensing deficiency during corneal infection. Invest Ophth Vis Sci 2004; 45 (06) 1897-1903
    CrossrefPubMedSearch in Google Scholar
  • 30 Truchado P, Gil-Izquierdo A, Tomas-Barberan F et al. Inhibition by chestnut honey of N-acyl-l-homoserine lactones and biofilm formation in Erwinia carotovora, Yersinia enterocolitica, and Aeromonas hydrophila . J Agric Food Chem 2009; 57 (23) 11186-11193
    CrossrefPubMedSearch in Google Scholar
  • 31 Bjarnsholt T, Jensen OP, Burmolle M et al. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 2005; 151: 373-383
    CrossrefPubMedSearch in Google Scholar
  • 32 Davies DG, Parsek MR, Pearson JP et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 1998; 280: 295-298
    CrossrefPubMedSearch in Google Scholar
  • 33 Rashid MH, Kornberg A. Inorganic polyphosphate is needed for swimming, swarming and twitching motilities of Pseudomonas aeruginosa . Proc Natl Acad Sci USA 2000; 97: 4885-4890
    CrossrefPubMedSearch in Google Scholar
  • 34 Skindersoe ME, Alhede M, Phipps R et al. Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa . Antimicrob Agents and Chemother 2008; 52: 3648-3663
    CrossrefPubMedSearch in Google Scholar
  • 35 Garske LA, Beatson SA, Leech AJ et al. Sub-inhibitory concentrations of ceftazidime and tobramycin reduce the quorum sensing signals of Pseudomonas aeruginosa . Pathology 2004; 36: 571-575
    CrossrefPubMedSearch in Google Scholar