Effect-Directed Synthesis of PhoP/PhoQ Inhibitors to Regulate Salmonella Virulence

Salmonella spp. are among the leading bacterial causes of foodborne infections. The PhoP/PhoQ two-component regulatory system serves as a master virulence regulator in Salmonella. Although PhoP/PhoQ represents an ideal target for disarming Salmonella virulence, it has very few inhibitors reported so...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2022-06, Vol.70 (22), p.6755-6763
Main Authors: Cabezudo, Ignacio, Lobertti, Carlos A., Véscovi, Eleonora García, Furlan, Ricardo L. E.
Format: Article
Language:English
Subjects:
Food Safety and Toxicology
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Summary:Salmonella spp. are among the leading bacterial causes of foodborne infections. The PhoP/PhoQ two-component regulatory system serves as a master virulence regulator in Salmonella. Although PhoP/PhoQ represents an ideal target for disarming Salmonella virulence, it has very few inhibitors reported so far. We describe a novel platform by which an inhibitor was selected out of around 185 compounds directly from reaction media containing thiosemicarbazones and mono-, di-, and trihydrazones. To achieve this, tandem library preparation, thin-layer chromatography (TLC) bioautography, and effect-directed deconvolution were applied. We illustrate the potential of this effect-directed synthesis for the identification of new useful bioactive compounds for the food field.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.2c01087