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RESEARCH ARTICLE
Contents Vol 71(9)

Alkyne-Substituted Fimbrolide Analogues as Novel Bacterial Quorum-Sensing Inhibitors

Nripendra Nath Biswas A , George M. Iskander A , Marcin Mielczarek A , Tsz Tin Yu A , David StC Black A and Naresh Kumar A B
+ Author Affiliations
- Author Affiliations

A School of Chemistry, UNSW Sydney, Sydney, NSW 2052, Australia.

B Corresponding author. Email: n.kumar@unsw.edu.au

Australian Journal of Chemistry 71(9) 708-715 https://doi.org/10.1071/CH18194
Submitted: 30 April 2018  Accepted: 13 July 2018   Published: 14 August 2018

Abstract

Gram-negative bacteria such as Pseudomonas aeruginosa use furanosyl diesters as autoinducers for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation, and antibiotic resistance. A range of natural and synthetic brominated furanones, i.e. fimbrolide derivatives, have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, several novel acetylene analogues of fimbrolides were synthesised in moderate to high yields via Sonogashira coupling reactions of brominated furanones 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 and 5-(dibromomethylene)-3-ethylfuran-2(5H)-one 5. The Sonogashira reaction of acetylenes on 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 was favoured at the C5 methylene bromide over the C4 bromide substituent. On biological testing, the most potent compounds 13 and 14 showed 82 and 98 % bacterial quorum-sensing inhibitory (QSI) activity against Pseudomonas aeruginosa reporter strain respectively.


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