Natural product rottlerin derivatives targeting quorum sensing

Dittu Suresh, Shekh Sabir, Tsz Tin Yu, Daniel Wenholz, Theerthankar Das, David St C Black, Naresh Kumar

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.

Original languageEnglish
Article number3745
Number of pages13
JournalMolecules
Volume26
Issue number12
DOIs
Publication statusPublished - 2 Jun 2021
Externally publishedYes

Keywords

  • Natural products
  • Pseudomonas aeruginosa
  • Pyranochromene chalcone
  • Quorum sensing inhibitors
  • Rottlerin

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