Quorum-Sensing Inhibitors

A rapid synthesis of carbon-14 labeled [l-14C]levulinic acid from simple building blocks has been demonstrated by Johansen and coworkers (Scheme 6.172) [324], In all three of the synthetic steps, starting from bromo[l-14C]acetic acid, microwave heating was used to accelerate the reactions, allowing a total preparation time of less than 1 h. The labeled levulinic acid was subsequently transformed into (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone in a bromination/oxidation sequence (not shown), a potent quorum sensing inhibitor. 

Rasmussen TB, Givskov M (2006) Quorum sensing inhibitors a bargain of effects. Microbiology 152 895-904... 

Vattem DA, Mihahk K, Crixell SH, McLean RJ. Dietary phytochemicals as quorum sensing inhibitors. Eitoterapia 2007 78 302— 310. 

Staphylococci are responsible for most of the nosocomial infections. Since these bacteria are resistant to several antibiotics, there is an urgent need for novel drugs against Staphylococci infections. Quorum-sensing inhibitors that block the cell-to-cell communication between Staphylococci and thereby inhibit their virulence could represent an alternative to antibiotics. A pharmacophore-based screening retrieved hamamelitannin (7, Figure 5.11) from the bark and leaves of Hamamelis virginiana. 

G., Ghiselli, R., Saba, V., Orlando, F., Shoham, M., and Balaban, N. (2008) Discovery of a quorum-sensing inhibitor of dmg-resistant staphylococcal infections by stmcture-based virtual screening. Molecular Pharmacology, 73, 1578-1586. 

In many cases, one may be interested in recovering either quorum-sensing signals from particular bacteria or potential quorum-sensing inhibitors (QSIs) from eukaryotic organisms or from microorganisms. For the isolation of QSIs from eukaryotes, whole materials are normally extracted for active compounds. 

Fig. 2. Elastase activity of Pseudomonas aeruginosa in the presence and absence of a quorum-sensing inhibitor (QSI). Samples were collected at 7, 8, and 22 h post inoculation in the presence of a quorum-sensing antagonist at 10 and 20 pg/mL. Elastase activity was determined on cell-free supernatants from the different time points and was normalized based on total protein concentration of the supernatants.

PAN J and REN D (2009) Quorum sensing inhibitors a patent overview. Expert Opin Therapeutic Patents, 19,1581-1601. 

PERSSON T, HANSEN T H, RASMUSSEN T B, SKINDERSOE M E, GIVSKOV M, NIELSEN J (2005) Rational design and synthesis of new quorum sensing inhibitors derived from acylated homoserine lactones and natural products from garhe. Org Biomol Chem, 3,253-262. 

TEASDALE M E, DONOVAN K A, FORSCHNER-DANCAUSE S R and ROWLEY D C (2011) Gram-positive marine bacteria as a potential resource for the discovery of quorum sensing inhibitors. Mar Biotechnol, 13, 722-732. 

Kociolek MG. Quorum-sensing inhibitors and biofilms. Anti-Infect Agents Med Chem 2009 8 315-26. htfp //dx.doi.org/10.2174/187152109789760117. 

Van Bambeke F, Glupczynski Y, Plesiat P, Pechere 1C, Tulkens PM (2003) Antibiotic efflux pumps in prokaryotic cells occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother 51 1055-1065 VanEtten HD, Mansfield JW, Bailey lA, Farmer EE (1994) Two classes of plant antibiotics phytoalexins versus phytoanticipins. Plant Cell 6 1191-1192 Vattem DA, MihaUk K, Ciixell SH, McLean RIC (2007) Dietary phytochemicals as quorum sensing inhibitors. Fitoterapia 78 302-310... 

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