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Molecules 2018, 23(6), 1385; https://doi.org/10.3390/molecules23061385

Cobalt Complex with Thiazole-Based Ligand as New Pseudomonas aeruginosa Quorum Quencher, Biofilm Inhibitor and Virulence Attenuator

1
LEPABE, Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, Porto 4200-465, Portugal
2
Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, Belgrade 11000, Serbia
3
Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, Belgrade 11000, Serbia
4
Institute of Chemistry, University of Tartu, Ravila 14a, Tartu 50411, Estonia
*
Author to whom correspondence should be addressed.
Received: 3 May 2018 / Revised: 30 May 2018 / Accepted: 7 June 2018 / Published: 8 June 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Pseudomonas aeruginosa is one of the most dreaded human pathogens, because of its intrinsic resistance to a number of commonly used antibiotics and ability to form sessile communities (biofilms). Innovative treatment strategies are required and that can rely on the attenuation of the pathogenicity and virulence traits. The interruption of the mechanisms of intercellular communication in bacteria (quorum sensing) is one of such promising strategies. A cobalt coordination compound (Co(HL)2) synthesized from (E)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)-4-(p-tolyl)thiazole (HL) is reported herein for the first time to inhibit P. aeruginosa 3-oxo-C12-HSL-dependent QS system (LasI/LasR system) and underling phenotypes (biofilm formation and virulence factors). Its interactions with a possible target, the transcriptional activator protein complex LasR-3-oxo-C12-HSL, was studied by molecular modeling with the coordination compound ligand having stronger predicted interactions than those of co-crystallized ligand 3-oxo-C12-HSL, as well as known-binder furvina. Transition metal group 9 coordination compounds may be explored in antipathogenic/antibacterial drug design. View Full-Text
Keywords: antibacterial resistance; antivirulence/antipathogenic compounds; biofilm prevention; cobalt complex; furvina; pyocyanin; pyoverdine; quorum sensing inhibition; transcriptional activator protein LasR antibacterial resistance; antivirulence/antipathogenic compounds; biofilm prevention; cobalt complex; furvina; pyocyanin; pyoverdine; quorum sensing inhibition; transcriptional activator protein LasR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Borges, A.; Simões, M.; Todorović, T.R.; Filipović, N.R.; García-Sosa, A.T. Cobalt Complex with Thiazole-Based Ligand as New Pseudomonas aeruginosa Quorum Quencher, Biofilm Inhibitor and Virulence Attenuator. Molecules 2018, 23, 1385.

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