Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the <i>Pseudomonas</i> Quinolone Signaling System

Theerthankar Das; Shekh Sabir; Ren Chen; Jessica Farrell; Frederik H. Kriel; Gregory S. Whiteley; Trevor O. Glasbey; Jim Manos; Mark D. P. Willcox; Naresh Kumar

doi:10.3390/molecules27041169

Molecules (Feb 2022)

Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the <i>Pseudomonas</i> Quinolone Signaling System

Theerthankar Das,
Shekh Sabir,
Ren Chen,
Jessica Farrell,
Frederik H. Kriel,
Gregory S. Whiteley,
Trevor O. Glasbey,
Jim Manos,
Mark D. P. Willcox,
Naresh Kumar

Affiliations

Theerthankar Das: Infection, Immunity and Inflammation, Charles Perkins Centre, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia
Shekh Sabir: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Ren Chen: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
Jessica Farrell: Infection, Immunity and Inflammation, Charles Perkins Centre, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia
Frederik H. Kriel: Whiteley Corporation, 19-23 Laverick Avenue, Tomago, NSW 2322, Australia
Gregory S. Whiteley: Whiteley Corporation, 19-23 Laverick Avenue, Tomago, NSW 2322, Australia
Trevor O. Glasbey: Whiteley Corporation, 19-23 Laverick Avenue, Tomago, NSW 2322, Australia
Jim Manos: Infection, Immunity and Inflammation, Charles Perkins Centre, Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia
Mark D. P. Willcox: School of Optometry and Vision Science, The University of New South Wales, Sydney, NSW 2052, Australia
Naresh Kumar: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia

DOI: https://doi.org/10.3390/molecules27041169
Journal volume & issue: Vol. 27, no. 4
p. 1169

Abstract

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Quorum-sensing (QS) systems of Pseudomonas aeruginosa are involved in the control of biofilm formation and virulence factor production. The current study evaluated the ability of halogenated dihydropyrrol-2-ones (DHP) (Br (4a), Cl (4b), and F (4c)) and a non-halogenated version (4d) to inhibit the QS receptor proteins LasR and PqsR. The DHP molecules exhibited concentration-dependent inhibition of LasR and PqsR receptor proteins. For LasR, all compounds showed similar inhibition levels. However, compound 4a (Br) showed the highest decrease (two-fold) for PqsR, even at the lowest concentration (12.5 µg/mL). Inhibition of QS decreased pyocyanin production amongst P. aeruginosa PAO1, MH602, ATCC 25619, and two clinical isolates (DFU-53 and 364707). In the presence of DHP, P. aeruginosa ATCC 25619 showed the highest decrease in pyocyanin production, whereas clinical isolate DFU-53 showed the lowest decrease. All three halogenated DHPs also reduced biofilm formation by between 31 and 34%. The non-halogenated compound 4d exhibited complete inhibition of LasR and had some inhibition of PqsR, pyocyanin, and biofilm formation, but comparatively less than halogenated DHPs.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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