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

被引:6
|
作者
Moreira, Thais A. [1 ]
Antolinez, Isabel V. [1 ]
Valenca, Wagner O. [1 ]
Roy, Sweta [2 ]
Ramirez, Isabela [2 ]
Barbosa, Luis C. A. [1 ]
Ren, Dacheng [3 ]
机构
[1] Univ Fed Minas Gerais, Dept Chem, Av Pres Antonio Carlos 6627,Campus Pampulha, BR-31270901 Belo Horizonte, MG, Brazil
[2] SUNY Syracuse, Dept Biomed & Chem Engn, Syracuse, NY 13244 USA
[3] SUNY Syracuse, Dept Biomed & Chem Engn, Civil & Environm Engn, Syracuse, NY 13244 USA
关键词
Cadiolides; Quorum sensing; Anti-biofilm agents; Alkynone; BROMINATED FURANONES; GENE-EXPRESSION; LACTONES; AUTOINDUCERS;
D O I
10.1016/j.bmcl.2021.128498
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
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页数:4
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