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Synthesis and Biological Evaluation of Novel Acyclic and Cyclic Glyoxamides as Bacterial Quorum Sensing and Biofilm Inhibitors

Abstract

Bacteria regulate the expression of various virulence factors and processes such as biofilm formation through a chemically-mediated communication mechanism calcd quorum sensing (QS). Bacterial biofilms contribute to antimicrobial resistance as they can protect bacteria embedded in their matrix from the effects of antibiotics. Thus, developing novel quorum sensing inhibitors, which can inhibit biofilm formation, is a viable strategy to combat antimicrobial resistance. We report herein the synthesis of novel acyclic and cyclic glyoxamide derivatives via ring-opening reactions of N-acylisatins. These compounds were evaluated for their quorum sensing inhibition (QSI) activity against P. aeruginosa MH602 and E. coli MT102. Compounds 20, 21 and 30 displayed the greatest QSI activity against P. aeruginosa MH602, with 71.5%, 71.5%, and 74% inhibition, respectively, at 250 µM. Compounds 18, 20 and 21 exhibited the greatest QSI activity against E. coli MT102, with 71.5%, 72.1% and 73.5% QSI activity, respectively. In addition, the biofilm inhibition activity was also investigated against P. aeruginosa and E. coli at 250 µM. The glyoxamide compounds 16, 18 and 19 exhibited 71.2%, 66.9%, and 66.5% inhibition of P. aeruginosa biofilms, respectively; whereas compounds 12, 20, and 22 showed the greatest inhibitory activity against E. coli biofilms with 87.9%, 90.8% and 89.5%, respectively. Finally, the determination of the in vitro toxicity against human MRC-5 lung fibroblast cells revealed that these novel glyoxamide compounds are non-toxic to human cells.

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Publication details

The article was received on 26 Apr 2017, accepted on 15 Jun 2017 and first published on 16 Jun 2017


Article type: Paper
DOI: 10.1039/C7OB01011G
Citation: Org. Biomol. Chem., 2017, Accepted Manuscript
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    Synthesis and Biological Evaluation of Novel Acyclic and Cyclic Glyoxamides as Bacterial Quorum Sensing and Biofilm Inhibitors

    S. Nizalapur, O. Kimyon, E. Yee, M. Bhadbhade, M. Manefield, M. D.P. Willcox, D. S. Black and N. Kumar, Org. Biomol. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7OB01011G

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