Cadiolide analogues and their precursors as new inhibitors of bacterial quorum sensing and biofilm formation. (1st February 2022)

• Record Type: Journal Article
• Authors: Moreira, Thais A.; Antolínez, Isabel V.; Valença, Wagner O.; Roy, Sweta; Ramirez, Isabela; Barbosa, Luiz C.A.; Ren, Dacheng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 57(2022)
• Publication Date: 2022-02-01
• Subjects: Cadiolides -- Quorum sensing -- Anti-biofilm agents -- Alkynone; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128498
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Cadiolides analogues are effective in inhibiting biofilm formation of E. coli . Cadiolides analogues interfered with the quorum sensing (QS) via AHL and AI-2. Compound 8b interfered with acyl-homoserine lactone mediated QS. Compound 9e interrupted the QS via autoinducer-2. Diarylynones are efficient in interfering with QS via both AHL and AI-2. 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.