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; Isabela Ramirez; Luiz C A Barbosa; Dacheng Ren

doi:10.1016/j.bmcl.2021.128498

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

Bioorg Med Chem Lett. 2022 Feb 1:57:128498. doi: 10.1016/j.bmcl.2021.128498. Epub 2021 Dec 9.

Authors

Thais A Moreira¹, Isabel V Antolínez¹, Wagner O Valença¹, Sweta Roy², Isabela Ramirez², Luiz C A Barbosa³, Dacheng Ren⁴

Affiliations

¹ Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
² Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA.
³ Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil. Electronic address: lcab@ufmg.br.
⁴ Department of Biomedical and Chemical Engineering, Civil and Environmental Engineering, and Biology, Syracuse University, Syracuse, NY 13244, USA. Electronic address: dren@syr.edu.

PMID: 34896477
DOI: 10.1016/j.bmcl.2021.128498

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.

Keywords: Alkynone; Anti-biofilm agents; Cadiolides; Quorum sensing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Butyrolactone / chemical synthesis
4-Butyrolactone / pharmacology*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / pharmacology*
Biofilms / drug effects*
Escherichia coli / drug effects
Escherichia coli / physiology
Microbial Sensitivity Tests
Pseudomonas aeruginosa / drug effects
Pseudomonas aeruginosa / physiology
Quorum Sensing / drug effects*
Stereoisomerism

Substances

Anti-Bacterial Agents
4-Butyrolactone