Synthesis and Biological Evaluation of Cajaninstilbene Acid and Amorfrutins A and B as Inhibitors of the <i>Pseudomonas aeruginosa</i> Quorum Sensing System

Xu, Xingjun; Zeng, Ting; Huang, Zhi-Xing; Xu, Xiaofang; Lin, Jing; Chen, Weimin

doi:10.1021/acs.jnatprod.8b00315

Cited by 24 publications

(16 citation statements)

References 33 publications

(78 reference statements)

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“…The synthesis of the target compounds was carried out starting from the 1‐bromo‐3,5‐dimethoxybenzene ( 1 ). After going through four steps routine reactions according to the literature methods (Ohba & Nakata, ; Xu et al, ), compound 2 was obtained. Isopentenylation was carried out in the condition of NaH and 3,3‐dimethylallyl bromide in anhydrous toluene at 70°C to obtain intermediate 3 .…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of 2‐hydroxyl‐4‐methoxyl‐3‐(3‐methylbut‐2‐en‐1‐yl)‐6‐(4‐phenylbenzoylamino)benzoic acid derivatives as antibacterial agents based on cajaninstilbene acid scaffold hopping

Zheng

Hou

et al. 2019

Drug Development Research

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The prevalence of multidrug resistance among clinically significant bacterial pathogens underlines a critical need for the development of new classes of antibacterial agents with novel structural scaffolds. Cajaninstilbene acid (CSA), which is isolated from pigeonpea leaves, has shown potent antibacterial activity. In this study, a series of 2‐hydroxyl‐4‐methoxyl‐3‐(3‐methylbut‐2‐en‐1‐yl)‐6‐(4‐phenylbenzoylamino)benzoic acid derivatives derived from CSA were designed and synthesized, and their antibacterial activities were evaluated. Several synthesized compounds exhibit better antibacterial activity than CSA against Staphylococcus aureus, Staphylococcus epidermidis, and two strains of methicillin‐resistant S. aureus. Meanwhile, the results of 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide assays illustrate the good selectivity between bacteria and normal cells of the most active compounds 6u and 6v. Furthermore, well combinations with bacterial RNA polymerase of 6u arising from docking study imply the possible mechanism of antibacterial activity of these synthetic compounds.

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Section: Resultsmentioning

confidence: 99%

Design and synthesis of 2‐hydroxyl‐4‐methoxyl‐3‐(3‐methylbut‐2‐en‐1‐yl)‐6‐(4‐phenylbenzoylamino)benzoic acid derivatives as antibacterial agents based on cajaninstilbene acid scaffold hopping

Zheng

Hou

et al. 2019

Drug Development Research

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“…Additionally, compound 8c showed suppression on expression of lasB-lacZ and pqsA-lacZ involved in the QS network pathway in P. aeruginosa. Thereby proving compound 8c as a promising lead with inhibition of QS and associated biofilm formation in P. aeruginosa [160,161].…”

Section: Cajaninstilbene Acid Derivativesmentioning

confidence: 96%

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

et al. 2022

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A biofilm is a community of stable microorganisms encapsulated in an extracellular matrix produced by themselves. Many types of microorganisms that are found on living hosts or in the environment can form biofilms. These include pathogenic bacteria that can serve as a reservoir for persistent infections, and are culpable for leading to a broad spectrum of chronic illnesses and emergence of antibiotic resistance making them difficult to be treated. The absence of biofilm-targeting antibiotics in the drug discovery pipeline indicates an unmet opportunity for designing new biofilm inhibitors as antimicrobial agents using various strategies and targeting distinct stages of biofilm formation. The strategies available to control biofilm formation include targeting the enzymes and proteins specific to the microorganism and those involved in the adhesion pathways leading to formation of resistant biofilms. This review primarily focuses on the recent strategies and advances responsible for identifying a myriad of antibiofilm agents and their mechanism of biofilm inhibition, including extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, and cyclic diguanylate inhibitors. Furthermore, we present the structure–activity relationships (SAR) of these agents, including recently discovered biofilm inhibitors, nature-derived bioactive scaffolds, synthetic small molecules, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids and antibiotics. We hope to fuel interest and focus research efforts on the development of agents targeting the uniquely complex, physical and chemical heterogeneous biofilms through a multipronged approach and combinatorial therapeutics for a more effective control and management of biofilms across diseases.

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“…Amorfrutins B and synthesized 4 8a – c ( Figure 15 a) were analogues of the natural products cajaninstilbene acid (CSA). They can inhibit the las system and las system-related virulence factors by competitively binding with the receptor OdDHL; they can also interrupt pqs and show biofilm inhibitory activity [ 109 , 110 ]. It was found that a caffeic acid derivative with phenolic hydroxyl group 49 ( Figure 15 a) played the same role as amorfrutins B.…”

Section: Inhibitors Acting On Multiple Qs Systemsmentioning

confidence: 99%

The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

Shen

Wang

et al. 2022

Marine Drugs

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The survival selection pressure caused by antibiotic-mediated bactericidal and bacteriostatic activity is one of the important inducements for bacteria to develop drug resistance. Bacteria gain drug resistance through spontaneous mutation so as to achieve the goals of survival and reproduction. Quorum sensing (QS) is an intercellular communication system based on cell density that can regulate bacterial virulence and biofilm formation. The secretion of more than 30 virulence factors of P. aeruginosa is controlled by QS, and the formation and diffusion of biofilm is an important mechanism causing the multidrug resistance of P. aeruginosa, which is also closely related to the QS system. There are three main QS systems in P. aeruginosa: las system, rhl system, and pqs system. Quorum-sensing inhibitors (QSIs) can reduce the toxicity of bacteria without affecting the growth and enhance the sensitivity of bacterial biofilms to antibiotic treatment. These characteristics make QSIs a popular topic for research and development in the field of anti-infection. This paper reviews the research progress of the P. aeruginosa quorum-sensing system and QSIs, targeting three QS systems, which will provide help for the future research and development of novel quorum-sensing inhibitors.

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Synthesis and Biological Evaluation of Cajaninstilbene Acid and Amorfrutins A and B as Inhibitors of the Pseudomonas aeruginosa Quorum Sensing System

Cited by 24 publications

References 33 publications

Design and synthesis of 2‐hydroxyl‐4‐methoxyl‐3‐(3‐methylbut‐2‐en‐1‐yl)‐6‐(4‐phenylbenzoylamino)benzoic acid derivatives as antibacterial agents based on cajaninstilbene acid scaffold hopping

Design and synthesis of 2‐hydroxyl‐4‐methoxyl‐3‐(3‐methylbut‐2‐en‐1‐yl)‐6‐(4‐phenylbenzoylamino)benzoic acid derivatives as antibacterial agents based on cajaninstilbene acid scaffold hopping

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

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