作者: Christine Deuschel ; Pierre Cosson ; Emilio Valentino ; Jean-Pierre Paccaud ; Stéphanie Braillard ; Aurore Lucas ; Eric Adam ; Mohammed Benghezal ; Michael G. Orchard ; Christine Burn

Antibiotic resistance continues to reduce the number of available antibiotics, increasing the need for novel antibacterial drugs. Since the seminal work of Sir Alexander Fleming, antibiotic identification has been based exclusively on the inhibition of bacterial growth in vitro. Recently, inhibitors of bacterial virulence which interfere with bacterial pathogenesis mechanisms have been proposed as an alternative to antibiotics, and a few were discovered using assays targeting specific virulence mechanisms. Here we designed a simple surrogate host model for the measurement of virulence and systematic discovery of anti-virulence molecules, based on the interaction of Tetrahymena pyriformis and Klebsiella pneumoniae cells. We screened a library of small molecules and identified several inhibitors of virulence. In a mouse pneumonia model we confirmed that an anti-virulence molecule displayed antibacterial activity against Klebsiella pneumoniae and Pseudomonas aeruginosa, by reducing dramatically the bacterial load in the lungs. This molecule did not inhibit bacterial growth in vitro but prevented biosynthesis of the Klebsiella capsule and lipopolysaccharides, a key requirement for virulence. Our results demonstrate that anti-virulence molecules represent an alternative to antibiotics and those can be discovered using non-animal host models.

2006-01-01·Heterocyclic Communications

SOLVENT FREE REGIOSELECTIVE HETEROCYCLIZATION OVER HZSM-5 ZEOLITE UNDER MICROWAVE IRRADIATION SYNTHESIS OF CONDENSED THIAZOLES

作者: Heravi, Majid M. ; Ghassemzadeh, Mitra ; Froomand, Mohammad ; Sadeghi, Majid M. ; Khaleghi, Shahnaz

3-Mercapto-1,2,4-triazin-5-one and 3-mercapto-1,2,4-triazoles were condensed with allyl bromide in the presence of base to afford the corresponding 3-allylthio compoundsThese compounds were regioselectively cyclized to give 2,3-dihydro-3,6-dimethylthiazolo[3,2-b][1,2,4]triazine and 2,3-dihydro-3-methylthiazolo[3,2-b][1,2,4]triazoles, resp.

2000-01-01·Phosphorus, Sulfur, and Silicon and the Related Elements

REGIOSELECTIVE S→N ALLYLIC TRANSPOSITION OF 3-ALLYLTHIO 1,2,4-TRIAZINONE WITHOUT SOLVENT, AND CATALYST UNDER MICROWAVE IRRADIATION

作者: M. M. Heravi ; M. A. Nooshabadi ; K. Aghapoor

The facile and regioselective cyclization of the (allylthio)triazinone I to the dihydrothiazolotriazinone II was catalyzed by H₂SO₄.[3,3]-Sigmatropic rearrangement of I under microwave irradiation gave the allyltriazinone III in fairly good yield.Treatment of III with concentrate H₂SO₄ gave the corresponding 2-methylthiazolo[2,3-c]triazin-1-one.

100 项与 ATH-18534 相关的药物交易

登录后查看更多信息