Reaction of (<i>Z</i>)-5-(Bromomethylene)thiophen-2(5<i>H</i>)-one with Some Nucleophiles in Search for New Biofilm Inhibitors

Benneche, T.; Chamgordani, Elahe Jafari; Scheie, Anne Aamdal

doi:10.1080/00397911.2011.602496

Cited by 5 publications

(2 citation statements)

References 6 publications

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“…Based on our data, we hypothesise that the thiophenones bind to one or more nucleophilic amino acid residues in LuxR by a similar addition-elimination mechanism ( Figure 5 ). We have recently shown that the 5-bromomethylene side-chain of TF101 reacts with thiols and amines under basic conditions by an addition-elimination mechanism [27] . Candidate nucleophilic amino acid residues include 4 cysteine residues in the C-terminal dimerisation domain of LuxR [28] .…”

Section: Discussionmentioning

confidence: 99%

A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis

et al. 2012

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Vibrio harveyi is amongst the most important bacterial pathogens in aquaculture. Novel methods to control this pathogen are needed since many strains have acquired resistance to antibiotics. We previously showed that quorum sensing-disrupting furanones are able to protect brine shrimp larvae against vibriosis. However, a major problem of these compounds is that they are toxic toward higher organisms and therefore, they are not safe to be used in aquaculture. The synthesis of brominated thiophenones, sulphur analogues of the quorum sensing-disrupting furanones, has recently been reported. In the present study, we report that these compounds block quorum sensing in V. harveyi at concentrations in the low micromolar range. Bioluminescence experiments with V. harveyi quorum sensing mutants and a fluorescence anisotropy assay indicated that the compounds disrupt quorum sensing in this bacterium by decreasing the ability of the quorum sensing master regulator LuxR to bind to its target promoter DNA. In vivo challenge tests with gnotobiotic brine shrimp larvae showed that thiophenone compound TF310, ( Z )-4-((5-(bromomethylene)-2-oxo-2,5-dihydrothiophen-3-yl)methoxy)-4-oxobutanoic acid, completely protected the larvae from V. harveyi BB120 when dosed to the culture water at 2.5 µM or more, whereas severe toxicity was only observed at 250 µM. This makes TF310 showing the highest therapeutic index of all quorum sensing-disrupting compounds tested thus far in our brine shrimp model system.

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Section: Discussionmentioning

confidence: 99%

A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis

et al. 2012

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“…It has been proposed that the 5-bromomethylene side-chain of quorum sensing-inhibiting thiophenones enables them to bind to nucleophilic amino acid residues in LuxR, the quorum sensing master regulator in V. harveyi , thereby decreasing the ability of LuxR to activate quorum sensing target genes 18 21 . Most of the thiophenones that inhibited quorum sensing V. harveyi (with A QSI > 2) also possess the bromomethylene side-chain, except for TF203, TF319 and TF342.…”

Section: Discussionmentioning

confidence: 99%

Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

Yang

Scheie

Benneche

et al. 2015

Sci Rep

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Disease caused by antibiotic resistant pathogens is becoming a serious problem, both in human and veterinary medicine. The inhibition of quorum sensing, bacterial cell-to-cell communication, is a promising alternative strategy to control disease. In this study, we determined the quorum sensing-disrupting activity of 20 thiophenones towards the quorum sensing model bacterium V. harveyi. In order to exclude false positives, we propose a new parameter (AQSI) to describe specific quorum sensing activity. AQSI is defined as the ratio between inhibition of quorum sensing-regulated activity in a reporter strain and inhibition of the same activity when it is independent of quorum sensing. Calculation of AQSI allowed to exclude five false positives, whereas the six most active thiophenones (TF203, TF307, TF319, TF339, TF342 and TF403) inhibited quorum sensing at 0.25 μM, with AQSI higher than 10. Further, we determined the protective effect and toxicity of the thiophenones in a highly controlled gnotobiotic model system with brine shrimp larvae. There was a strong positive correlation between the specific quorum sensing-disrupting activity of the thiophenones and the protection of brine shrimp larvae against pathogenic V. harveyi. Four of the most active quorum sensing-disrupting thiophenones (TF 203, TF319, TF339 and TF342) were considered to be promising since they have a therapeutic potential of at least 10.

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ChemInform Abstract: Reaction of (Z)‐5‐(Bromomethylene)thiophen‐2(5H)‐one with Some Nucleophiles in Search for New Biofilm Inhibitors.

2013

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Reaction of (Z)-5-(Bromomethylene)thiophen-2(5H)-one with Some Nucleophiles in Search for New Biofilm Inhibitors. -The nucleophilic substitution of the bromo substituent in title compound (I) is studied. The reaction fails with ammonium acetate or potassium cyanate and leads in fact to dimeric and trimeric ring opening products like (XI) and (XII). Actually, this reaction represents a stereospecific access to penta--2,4-dienoates. Selected substitution products are tested for their biofilm inhibition activity. Slight activity is observed only for aromatic sulfur compounds, e.g. (IIId). -(BENNECHE*, T.; CHAMGORDANI, E. J.; SCHEIE, A. A.; Synth. Commun. 43 (2013) 3, 431-437, http://dx.

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Reaction of (Z)-5-(Bromomethylene)thiophen-2(5H)-one with Some Nucleophiles in Search for New Biofilm Inhibitors

Cited by 5 publications

References 6 publications

A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis

A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis

Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

ChemInform Abstract: Reaction of (Z)‐5‐(Bromomethylene)thiophen‐2(5H)‐one with Some Nucleophiles in Search for New Biofilm Inhibitors.

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