Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa

Hansen, Mette Reimert; Jakobsen, Tim Holm; Bang, Claus G.; Cohrt, A. Emil; Hansen, Casper Lykke; Clausen, Janie Regitse Waël; Quement, Sebastian Thordal Le; Tolker‐Nielsen, Tim; Givskov, Michael; Nielsen, Thomas E.

doi:10.1016/j.bmc.2015.01.038

Cited by 35 publications

(26 citation statements)

References 40 publications

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“…Several compounds were screened for their anti-QS activity. Heterocyclic nitrogenous compounds were tested broadly as anti-QS inhibitors [18][19][20], particularly pyrazine derivatives that were successfully used to modulate QS in Vibrio cholerae [18] and triazole derivatives that showed efficient anti-QS activity [21][22][23]. Sitagliptin, a pyrazine derivative with triazole moiety, is a hypoglycaemic agent for type II diabetes patients via inhibition of dipeptidyl-peptidase IV [35].…”

Section: Discussionmentioning

confidence: 99%

“…Many triazole moiety-containing compounds have the capability to bind various biological targets via hydrogen bonding and dipole interactions [19,20]. Interestingly, triazole derivatives showed anti-QS activity, especially those containing analogs of natural N-acyl Lhomoserine lactone, thymidine and isoxazole structures that strongly modulated bacterial QS and can be used as potential lead structures for the development of effective QS inhibitors [21][22][23]. In our previous work, diverse compounds which can modulate QS to curtail bacterial pathogenesis were screened.…”

Section: Introductionmentioning

confidence: 99%

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Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Abbas

Hegazy

2020

PLoS ONE

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Background Serratia marcescens is an emerging pathogen that causes a variety of health care associated infections. S. marcescens is equipped with an arsenal of virulence factors such as biofilm formation, swimming and swarming motilities, prodigiosin, protease and others which enable it to initiate and cause the infection. These virulence factors are orchestrated under the umbrella of an intercellular communication system named Quorum sensing (QS). QS allows bacterial population to synchronize the expression of virulence genes upon detection of a chemical signaling molecule. Targeting bacterial virulence is a promising approach to attenuate bacteria and enhances the ability of immune system to eradicate the bacterial infection. Drug repurposing is an advantageous strategy that confers new applications for drugs outside the scope of their original medical use. This promising strategy offers the use of safe approved compounds, which potentially lowers the costs and shortens the time than that needed for development of new drugs. Sitagliptin is dipeptidyl peptidase-4 (DPP-4) inhibitor, is used to treat diabetes mellitus type II as it increases the production of insulin and decreasing the production of glucagon by the pancreas. We aimed in this study to repurpose sitagliptin, investigating the anti-virulence activities of sitagliptin on S. marcescens. Methods The effect of sub-inhibitory concentrations of sitagliptin on virulence factors; protease, prodigiosin, biofilm formation, swimming and swarming motilities was estimated phenotypically. The qRT-PCR was used to show the effect of sitagliptin on the expression of QS-regulated virulence genes. The in-vivo protective activity of sitagliptin on S. marcescens pathogenesis was evaluated on mice. Results Sitagliptin (1 mg/ml) significantly reduced the biofilm formation, swimming and swarming motilities, prodigiosin and protease. The qRT-PCR confirmed the effect on virulence as shown by down regulating the expression of fimA, fimC, flhC, flhD, bsmB, rssB, rsmA, pigP,

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Abbas

Hegazy

2020

PLoS ONE

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“…223 1,5-Triazole derivatives have shown activity against numerous cancer cell lines, 205,215,[224][225][226][227] and against the parasites Trypanosoma cruzi 70,228 and Plasmodium falciparum. 205 They have also been employed in the search for new antimicrobiotics 229 and antifungal agents. 230 Institute's panel screen (NCI-60 panel) compared to vorinostat and dasatinib.…”

Section: Target-oriented Medicinal Chemistrymentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years. CONTENTS

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“…[13][14][15] A number of QS-modulating ligands have been designed and synthesized by mimicking the natural auto-inducers such as OdDHL, BHL or PQS. [16][17][18][19][20][21][22][23][24][25][26][27] According to structure-activity relationship (SAR) studies of the synthesized QS ligands, the hydrophilic group (e.g., lactone, quinolone) and the lipophilic alkyl chains are essential for the QS-modulating activity. [28][29][30][31][32][33] Inhibitors that block the complex formation between auto-inducers and the cognate receptors could downregulate the transcription of QS-associated genes and diminish or halt the virulence of P. aeruginosa.…”

mentioning

confidence: 99%

Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Park

Kim

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa

Cited by 35 publications

References 40 publications

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

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