Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in
            <i>Pseudomonas aeruginosa</i>

Shen, Mo; Li, Qiaoqiang; Yang, Zhikun; Li, Yasheng; Ye, Xinyi; Wang, Hong

doi:10.1080/14756366.2023.2175820

Cited by 7 publications

(4 citation statements)

References 41 publications

(34 reference statements)

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“…Elastase activity was measured using the Elastin-Congo Red (ECR) assays, , with modifications. Briefly, overnight culture of P. aeruginosa PAO1 in LB medium was standardized to a final optical density at 600 nm (OD 600 ) of 0.01.…”

Section: Methodsmentioning

confidence: 99%

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3-Hydroxypyridin-4(1H)-one Derivatives as pqs Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in Pseudomonas aeruginosa

Miao,

Zhang,

Yang

et al. 2023

J. Med. Chem.

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The development of quorum sensing inhibitors capable of decreasing the production of virulence factors is an effective strategy to overcome resistance in Pseudomonas aeruginosa due to the less selective pressure exerted on bacteria. In this study, a series of 3-hydroxypyridin-4(1H)-one derivatives bearing a 4-aminomethyl-1,2,3-triazole linker were designed and synthesized as antivirulence agents against P. aeruginosa. The most potent derivative 16e was identified as a selective inhibitor of the pqs system (IC 50 = 3.7 μM) and its related virulence factor pyocyanin (IC 50 = 2.7 μM). In addition, 16e exhibited moderate biofilm inhibition and significant inhibition of P. aeruginosa motility phenotypes with low cytotoxicity. Compound 16e showed an obvious antibacterial synergistic effect in combination with antibiotics such as ciprofloxacin and tobramycin in in vitro and in vivo Caenorhabditis elegans infection models. Overall, the excellent antivirulence properties of compound 16e make it a potential antibiotic adjuvant for the treatment of P. aeruginosa infections that may be advanced into preclinical development in the future.

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Section: Methodsmentioning

confidence: 99%

“…Elastase activity was measured using the Elastin-Congo Red (ECR) assays, 54,55 were incubated for 24 h at 37 °C under shaking conditions (200 rpm). The cultures were centrifuged for 10 min at 10,000 rpm and 4 °C.…”

Section: Elastase Assaymentioning

confidence: 99%

3-Hydroxypyridin-4(1H)-one Derivatives as pqs Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in Pseudomonas aeruginosa

Miao,

Zhang,

Yang

et al. 2023

J. Med. Chem.

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“…The formation of bio lm was discovered to be the primary cause of cystic pulmonary brosis (CF) brought on by P. aeruginosa( ). The appearance of bio lm shields bacteria from dehydration, chemicals, and antibacterial agents and allows them to elude the body's immune system (Yan et al 2019;Mao et al 2023). Berberine hydrochloride exhibits a lower concentration of 64µg/ml against P. aeruginosa bio lm, in contrast to existing antibiotics like CIP, which has an MIC of 512µg/ml (Wannigama et al 2020).…”

Section: Disscussionmentioning

confidence: 99%

Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa

Liu,

Tang,

Jiang

et al. 2023

Preprint

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The growing prevalence of extensive drug-resistant and pan-drug resistant Pseudomonas aeruginosa (P. aeruginosa) has become a significant concern for global public health, particularly due to the formation of biofilms. Consequently, it is crucial to explore the development of novel antimicrobials that specifically target P. aeruginosa and its biofilms. Here we found a natural compound named berberine hydrochloride, subsequently, Crystalline violet staining and Confocal laser scanning microscope further demostrated that berberine hydrochloride suppress biofilm. Additionally, it was found that the expression of pslA and other biofilm-related genes were downregulated. Compared with available antibiotics, berberine hydrochloride has multiple modes of action in P. aeruginosa. The antimicrobial mechanism showed that berberine hydrochloride might have antimicrobial effects by damaging bacterial cell membranes, generating reactive oxygen species (ROS) and lowering intracellular adenosine triphosphate (ATP). Futhermore, berberine hydrochloride possesses various attributes, including minimal cytotoxicity and reduced susceptibility to drug resistance. In a mice peritonitis model, it was reported to inhibit the growth of P. aeruginosa significantly and displayed high bacteriostatic action. Collectively, the berberine hydrochloride is a safe and effective antibacterial agent for inhibiting P. aeruginosa.

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“…Both allicin and ajoene have sulfoxide structures, and we hypothesized that benzoheterocyclic sulfoxide might also have quorum sensing activity. In our previous work, we synthesized a series of benzoheterocyclic sulfoxide derivatives in the hope of finding new lead compounds to inhibit the quorum sensing of P. aeruginosa [36]. In addition, benzoheterocyclic sulfoxide derivatives in a planar π system in three-dimensional space structures were analyzed.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Phenyloxadiazole Sulfoxide Derivatives as Potent Pseudomonas aeruginosa Biofilm Inhibitors

Shen

et al. 2023

Molecules

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With the development of antimicrobial agents, researchers have developed new strategies through key regulatory systems to block the expression of virulence genes without affecting bacterial growth. This strategy can minimize the selective pressure that leads to the emergence of resistance. Quorum sensing (QS) is an intercellular communication system that plays a key role in the regulation of bacterial virulence and biofilm formation. Studies have revealed that the QS system controls 4–6% of the total number of P. aeruginosa genes, and quorum sensing inhibitors (QSIs) could be a promising target for developing new prevention and treatment strategies against P. aeruginosa infection. In this study, four series of phenyloxadiazole and phenyltetrazole sulfoxide derivatives were synthesized and evaluated for their inhibitory effects on P. aeruginosa PAO1 biofilm formation. Our results showed that 5b had biofilm inhibitory activity and reduced the production of QS-regulated virulence factors in P. aeruginosa. In addition, silico molecular docking studies have shown that 5b binds to the P. aeruginosa QS receptor protein LasR through hydrogen bond interaction. Preliminary structure–activity relationship and docking studies show that 5b has broad application prospects as an anti-biofilm compound, and further research will be carried out in the future to solve the problem of microbial resistance.

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Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa

Cited by 7 publications

References 41 publications

3-Hydroxypyridin-4(1H)-one Derivatives as pqs Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in Pseudomonas aeruginosa

3-Hydroxypyridin-4(1H)-one Derivatives as pqs Quorum Sensing Inhibitors Attenuate Virulence and Reduce Antibiotic Resistance in Pseudomonas aeruginosa

Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa

Design, Synthesis, and Biological Evaluation of Phenyloxadiazole Sulfoxide Derivatives as Potent Pseudomonas aeruginosa Biofilm Inhibitors

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