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

## TL;DR

This study identifies cashew nut shell derivatives as potential inhibitors of a key enzyme in Pseudomonas aeruginosa, which could help reduce its virulence.

## Contribution

The discovery of anacardic acid derivatives as PaPhzD ligands and their effect on pyocyanin production is novel.

## Key findings

- Compounds 2 and 4 reduced pyocyanin production and swarming motility in Pseudomonas aeruginosa.
- The compounds did not affect bacterial growth or biofilm formation.
- The study suggests distinct SAR requirements for PaPhzD and PPAR ligands.

## Abstract

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.