Derivatives of the Cashew Nut Shell Liquid as Ligands of Pseudomonas aeruginosa Phenazine Protein D (PaPhzD)

Pseudomonas aeruginosa isochorismatase PhzD (PaPhzD) is key to the biosynthesis of pyocyanin (PYO), a virulence factor facilitating pathogen infection and survival within the host. To date, no ligands of PaPhzD have been reported. Leveraging the chemical similarity between anacardic acid derivatives and the enzyme’s natural substrate, three compounds (2, 3, and 4) were identified as low to submicromolar PaPhzD ligands, while compounds 2 and 4 reduced pyocyanin production (Cohen′d = −2.56 and −2.69, respectively) and swarming motility (Cohen′d = −0.91 and −0.95, respectively) at 100 μM, without affecting bacterial growth or biofilm formation (p > 0.05). Our results suggest that compounds binding to PaPhzD or PPAR have distinct SAR requirements, suggesting that they represent a promising scaffold for developing PaPhzD inhibitors.

• Publication year

  2025

• Venue

  ACS Omega

• Publication date

  2025-12-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/acsomega.5c08941PMID 41487265PMCID 12756723
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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