5-Arylidene-2-phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors

Rosaria Ottanà, Rosanna Maccari, Rosella Ciurleo, Paolo Paoli, Michela Jacomelli, Giampaolo Manao, Guido Camici, Christian Laggner, Thierry Langer

Research output: Contribution to journalArticlepeer-review

Abstract

As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-phenylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a-d, f) showed interesting inhibition levels in the low micromolar range. The 5-arylidene moiety of acids 4 proved to markedly influence the potency of these inhibitors. Molecular modeling experiments inside the binding sites of both enzymes were performed.

Original languageEnglish
Pages (from-to)1928-1937
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

Keywords

  • 5-Arylidene-2-phenylimino-4-thiazolidinones
  • Inhibitors
  • LMW-PTP
  • Protein tyrosine phosphatases
  • PTP1B

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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