A highly versatile convergent/divergent “onion peel” synthetic strategy toward potent multivalent glycodendrimers

Both convergent and divergent strategies for the synthesis of “onion peel” glycodendrimers are reported which resulted in one of the best multivalent ligands known against the virulent factor from a bacterial lectin isolated from Pseudomonas aeruginosa.

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Natural Product Rottlerin Derivatives Targeting Quorum Sensing

Molecules ◽

10.3390/molecules26123745 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3745

Author(s):

Dittu Suresh ◽

Shekh Sabir ◽

Tsz Tin Yu ◽

Daniel Wenholz ◽

Theerthankar Das ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Growth Inhibition ◽

Natural Product ◽

Bacterial Growth ◽

Inhibitory Activity ◽

Chalcone Derivatives ◽

Synthetic Strategy ◽

The Mannich Reaction ◽

Bacterial Growth Inhibition

Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of Pseudomonas aeruginosa. Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, 8b and 8d, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.

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Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low-Nanomolar Multivalent Ligands

Chemistry - A European Journal ◽

10.1002/chem.201602047 ◽

2016 ◽

Vol 22 (33) ◽

pp. 11785-11794 ◽

Cited By ~ 19

Author(s):

Shuai Wang ◽

Lucie Dupin ◽

Mathieu Noël ◽

Cindy J. Carroux ◽

Louis Renaud ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Rational Design ◽

Multivalent Ligands

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Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.10.206 ◽

2014 ◽

Vol 10 ◽

pp. 1981-1990 ◽

Cited By ~ 6

Author(s):

Meriem Smadhi ◽

Sophie de Bentzmann ◽

Anne Imberty ◽

Marc Gingras ◽

Raoudha Abderrahim ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Multivalent Ligands ◽

Biological Probes

Readily accessible, low-valency glycoclusters based on a triazine core bearing D-galactose and L-fucose epitopes are able to inhibit biofilm formation by Pseudomonas aeruginosa. These multivalent ligands are simple to synthesize, are highly soluble, and can be either homofunctional or heterofunctional. The galactose-decorated cluster shows good affinity for Pseudomonas aeruginosa lectin lecA. They are convenient biological probes for investigating the roles of lecA and lecB in biofilm formation.

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