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 language | English |
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Pages (from-to) | 1928-1937 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 17 |
Issue number | 5 |
DOIs | |
Publication status | Published - 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