1. Synthetic chalcones and sulfonamides as new classes of Yersinia enterocolitica YopH tyrosine phosphatase inhibitors.
- Author
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Martins PG, Menegatti AC, Chiaradia-Delatorre LD, de Oliveira KN, Guido RV, Andricopulo AD, Vernal J, Yunes RA, Nunes RJ, and Terenzi H
- Subjects
- Bacterial Outer Membrane Proteins isolation & purification, Bacterial Outer Membrane Proteins metabolism, Chalcones chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Kinetics, Models, Molecular, Molecular Structure, Protein Tyrosine Phosphatases isolation & purification, Protein Tyrosine Phosphatases metabolism, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Structure-Activity Relationship, Sulfonamides chemistry, Bacterial Outer Membrane Proteins antagonists & inhibitors, Chalcones chemical synthesis, Chalcones pharmacology, Enzyme Inhibitors pharmacology, Protein Tyrosine Phosphatases antagonists & inhibitors, Sulfonamides chemical synthesis, Sulfonamides pharmacology, Yersinia enterocolitica enzymology
- Abstract
YopH plays a relevant role in three pathogenic species of Yersinia. Due to its importance in the prevention of the inflammatory response of the host, this enzyme has become a valid target for the identification and development of new inhibitors. In this work, an in-house library of 283 synthetic compounds was assayed against recombinant YopH from Yersinia enterocolitica. From these, four chalcone derivatives and one sulfonamide were identified for the first time as competitive inhibitors of YopH with binding affinity in the low micromolar range. Molecular modeling investigations indicated that the new inhibitors showed similar binding modes, establishing polar and hydrophobic contacts with key residues of the YopH binding site., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
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