Design, synthesis and evaluation of oxazolopyridinone derivatives as quorum sensing inhibitors

Chen, Weijin; Zhang, Panpan; Guo, Ting; Gu, Xiaotong; Bai, Bingfang; Zhang, Shenyan; Chang, Xiaohong; Wang, Yingmei; Ma, Shutao

doi:10.1016/j.bioorg.2022.106266

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…So, we used prodigiosin inhibition rates to evaluate the QSI and antibiofilm of indol-isonitrile derivatives against S. marcescens. According to similar work reported (Chen et al 2023). Our results indicated that IMBI could inhibit prodigiosin production dramatically, that is to say, it may be a potent QS inhibition activity.…”

Section: Discussionsupporting

confidence: 81%

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Yang

Wang

Tang

et al. 2023

Preprint

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Quorum sensing (QS) inhibition is recognized as a novel drug target for infections caused by drug-resistant pathogens and is an attractive strategy for the development of antipathogenic agents. Herein, we designed and synthesized three parts of3-(2-isocyanobenzyl)-1H-indole derivatives and evaluated their activity as novel quorum sensing inhibitors (QSIs). We found that 3-(2-isocyanobenzyl)-1H-indole derivatives showed promising QS inhibitory activity in the minimum inhibitory concentrations (MICs), biofilm and prodigiosin inhibition assays in Serratia marcescens. In particular, 3-(2-isocyano-6-methylbenzyl)-1H-indole(IMBI, 32) was the best candidate by biofilm and prodigiosin inhibition assays screening strategies. Further studies demonstrated, exposureIMBI (1.56 μg/mL, 1/8MICs) to S. marcescens NJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment (1.56 μg/mL) on S. marcescens NJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of biofilms up to 40% as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscope (CLSM). For interference of virulence factors in S. marcescens NJ01, IMBI (3.12 μg/mL, 1/4MICs) inhibited the activity of protease, and extracellular polysaccharides (EPS)by 17% and 51% respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expressions of QS- and biofilm-related genes bsmA,pigP, flhC, rssB, rsmA, and fimC by 0.13-fold to 1.46-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. Most importantly, the biofilms of S. marcescens NJ01 were markedly reduced by 50% under IMBI (0.39 μg/mL, 1/32MICs)combining with 0.15 μg/mL kalamycin (KAN). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors against S. marcescens. IMBI could be developed as an effective QS inhibitor and anti-biofilm agent to restore or improve drug sensitivity for drug-resistant pathogens.

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Section: Discussionsupporting

confidence: 81%

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Yang

Wang

Tang

et al. 2023

Preprint

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“…Followingly, the effect of indole-isonitrile compounds on prodigiosin, the key pathogenic factor of S. marcescens, was investigated to assess their QSI and antibiofilm activity. 41 Prodigiosin is essentially a crucial virulent factor controlled by QS and plays a vital role in invasion, survival, and pathogenicity. 14 We investigated the prodigiosin inhibition rates of S. marcescens to evaluate the QSI and antibiofilm properties of indole-isonitrile derivatives.…”

Section: ■ Resultsmentioning

confidence: 99%

“…Interestingly, IMBI exhibited an excellent inhibition effect on S. marcescens NJ01 at 1/4MICs (48%). Followingly, the effect of indole-isonitrile compounds on prodigiosin, the key pathogenic factor of S. marcescens , was investigated to assess their QSI and antibiofilm activity . Prodigiosin is essentially a crucial virulent factor controlled by QS and plays a vital role in invasion, survival, and pathogenicity .…”

Section: Discussionmentioning

confidence: 99%

Developing 3-(2-Isocyano-6-methylbenzyl)-1H-indole Derivatives to Enhance the Susceptibility of Serratia marcescens by Occluding Quorum Sensing

Wang,

Yang,

Durairaj

et al. 2023

ACS Infect. Dis.

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Quorum sensing (QS) inhibition is recognized as a novel antimicrobial target for infections caused by drug-resistant pathogens and is an attractive strategy for antipathogenic agent development. We designed and synthesized three parts of 3-(2isocyanobenzyl)-1H-indole derivatives and tested their activity as novel quorum sensing inhibitors (QSIs). 3-(2-Isocyanobenzyl)-1H-indole derivatives demonstrated promising QS, biofilms, and prodigiosin inhibitory activities against Serratia marcescens at subminimum inhibitory concentrations (sub-MICs). In particular, 3-(2-isocyano-6-methylbenzyl)-1H-indole (IMBI, 32) was identified as the best candidate based on several screening assays, including biofilm and prodigiosin inhibition. Further studies demonstrated that exposure to IMBI at 1.56 μg/mL to S. marcescens NJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment on S. marcescens NJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of the biofilms by up to 40%, as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). For interference of virulence factors in S. marcescens NJ01, IMBI at 3.12 μg/mL inhibited the activity of protease and extracellular polysaccharides (EPS) by 17% and 51%, respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expression of QS-and biofilm-related genes f imA, bsmA, pigP, f lhC, rssB, f imC, and rsmA by 1.02-to 2.74-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. The biofilms of S. marcescens NJ01 were markedly reduced by 50% when IMBI (0.39 μg/mL) was combined with kanamycin (0.15 μg/mL). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors of S. marcescens. IMBI has all the potential to be developed as an effective and efficient QS inhibitor and antibiofilm agent in order to restore or improve antimicrobial drug sensitivity.

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“…107−109 Moreover, certain five-membered lactone compounds and benzoxazolone compounds have also been employed as QSIs to mitigate biofilm infections. 110,111 In addition to these small molecule AIP analogues, there exist macromolecular AIP QSIs referred to as AIP QS quenching antibodies. 54,112 These antibodies rapidly obstruct the AIP-based QS system, effectively reducing the immune response of host cells.…”

Section: Autoinducer Analogues Ahl Analoguesmentioning

confidence: 99%

“…Noteworthy among synthetic AIP analogues is AIP-III D4A, a heptapeptide compound resembling AIP-III but boasting improved stability . Additionally, AIP-III nN2, AIP-III nF5, and tAIP-III D2A are AIP-III analogues, all capable of inhibiting the activity of the AgrC receptor protein in S. aureus , consequently disrupting the QS system. − Moreover, certain five-membered lactone compounds and benzoxazolone compounds have also been employed as QSIs to mitigate biofilm infections. , In addition to these small molecule AIP analogues, there exist macromolecular AIP QSIs referred to as AIP QS quenching antibodies. , These antibodies rapidly obstruct the AIP-based QS system, effectively reducing the immune response of host cells.…”

Section: Qs and Qsismentioning

confidence: 99%

Disruption of Communication: Recent Advances in Antibiofilm Materials with Anti-Quorum Sensing Properties

Qu,

Zou,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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Biofilm contamination presents a significant threat to public health, the food industry, and aquatic/marine-related applications. In recent decades, although various methods have emerged to combat biofilm contamination, the intricate and persistent nature of biofilms makes complete eradication challenging. Therefore, innovative alternative solutions are imperative for addressing biofilm formation. Instead of solely focusing on the eradication of mature biofilms, strategically advantageous measures involve the delay or prevention of biofilm formation on surfaces. Quorum sensing, a communication system enabling bacteria to coordinate their behavior based on population density, plays a pivotal role in biofilm formation for numerous microbial species. Materials possessing antibiofilm properties that target quorum sensing have gained considerable attention for their potential to prevent biofilm formation. This Review consolidates recent research progress on the utilization of materials with antiquorum sensing properties for combating biofilm formation. These materials can be categorized into three distinct types: (i) antibiofilm nanomaterials, (ii) antibiofilm surfaces, and (iii) antibiofilm hydrogels with antiquorum sensing capabilities. Finally, the Review concludes with a brief discussion of current challenges and outlines potential avenues for future research.

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Design, synthesis and evaluation of oxazolopyridinone derivatives as quorum sensing inhibitors

Cited by 12 publications

References 26 publications

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Synthesized 3-(2-isocyano-6-methylbenzyl)-1H-indole Enhanced Susceptibility of Serratia marcescens to Kanamycinby Occluding Quorum Sensing

Developing 3-(2-Isocyano-6-methylbenzyl)-1H-indole Derivatives to Enhance the Susceptibility of Serratia marcescens by Occluding Quorum Sensing

Disruption of Communication: Recent Advances in Antibiofilm Materials with Anti-Quorum Sensing Properties

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