Cadiolide analogues and their precursors as new inhibitors of bacterial quorum sensing and biofilm formation

Thais A. Moreira, Isabel V. Antolínez, Wagner O. Valença, Sweta Roy, Luiz C.A. Barbosa, Dacheng Ren

Research output: Contribution to journalArticlepeer-review

Abstract

Bacterial quorum sensing (QS) and biofilm formation are promising targets for developing new therapies to treat chronic infections. Herein, we report the stereoselective synthesis of 18 new analogs of natural cadiolides. Among the new compounds, substances 8b, 8f, 8i, 9a, 9b and 9e completely inhibited the biofilm formation of Escherichia coli RP347 in vitro. In addition, compound 8b interfered acyl-homoserine lactone (AHL) mediated QS, while 9e interrupted the QS via autoinducer-2 (AI-2). Biological assays also revealed that synthetic intermediates alkynones are potent inhibitors of AI-2 and AHL-mediated QS. These results indicate that cadiolides and alkynones are good candidates for further structural modification for a new generation of more potent antimicrobial agents.

Original languageEnglish (US)
Article number128498
JournalBioorganic and Medicinal Chemistry Letters
Volume57
DOIs
StatePublished - Feb 1 2022

Keywords

  • Alkynone
  • Anti-biofilm agents
  • Cadiolides
  • Quorum sensing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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