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

doi:10.1016/j.bmcl.2021.128498

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 journal › Article › peer-review

5 Scopus citations

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 language	English (US)
Article number	128498
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	57
DOIs	https://doi.org/10.1016/j.bmcl.2021.128498
State	Published - 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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10.1016/j.bmcl.2021.128498

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title = "Cadiolide analogues and their precursors as new inhibitors of bacterial quorum sensing and biofilm formation",

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",

author = "Moreira, {Thais A.} and Antol{\'i}nez, {Isabel V.} and Valen{\c c}a, {Wagner O.} and Sweta Roy and Barbosa, {Luiz C.A.} and Dacheng Ren",

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T1 - Cadiolide analogues and their precursors as new inhibitors of bacterial quorum sensing and biofilm formation

AU - Moreira, Thais A.

AU - Antolínez, Isabel V.

AU - Valença, Wagner O.

AU - Roy, Sweta

AU - Barbosa, Luiz C.A.

AU - Ren, Dacheng

PY - 2022/2/1

Y1 - 2022/2/1

N2 - 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.

AB - 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.

KW - Alkynone

KW - Anti-biofilm agents

KW - Cadiolides

KW - Quorum sensing

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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