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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2009.01.044 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Druggable targets of protein tyrosine phosphatase Family, viz. PTP1B, SHP2, Cdc25, and LMW-PTP: Current scenario on medicinal Attributes, and SAR insights.
Bioorg Chem
March 2024
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga 142 001, (Punjab), India. Electronic address:
Protein tyrosine phosphatases (PTPs) are the class of dephosphorylation enzymes that catalyze the removal of phosphate groups from tyrosine residues on proteins responsible for various cellular processes. Any disbalance in signal pathways mediated by PTPs leads to various disease conditions like diabetes, obesity, cancers, and autoimmune disorders. Amongst the PTP superfamily, PTP1B, SHP2, Cdc25, and LMW-PTP have been prioritized as druggable targets for developing medicinal agents.
View Article and Find Full Text PDFDifferential impact of cold and hot tea extracts on tyrosine phosphatases regulating insulin receptor activity: a focus on PTP1B and LMW-PTP.
Eur J Nutr
June 2022
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Morgagni 50, 50134, Florence, Italy.
Purpose: The impact of tea constituents on the insulin-signaling pathway as well as their antidiabetic activity are still debated questions. Previous studies suggested that some tea components act as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors. However, their nature and mechanism of action remain to be clarified.
View Article and Find Full Text PDFSynthesis, biological activity and structure-activity relationships of new benzoic acid-based protein tyrosine phosphatase inhibitors endowed with insulinomimetic effects in mouse C2C12 skeletal muscle cells.
Eur J Med Chem
January 2014
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Sezione di Scienze Biochimiche, University of Firenze, Viale Morgagni 50, 50134 Firenze, Italy.
Insulin resistance is a complex altered metabolic condition characterized by impaired insulin signaling and implicated in the pathogenesis of serious human diseases, such as diabetes, obesity, neurodegenerative pathologies. In pursuing our aim to identify new agents able to improve cellular insulin sensitivity, we have synthesized new 4-[(5-arylidene-4-oxo-2-phenylimino/oxothiazolidin-3-yl)methyl]benzoic acids (5, 8) and evaluated their inhibitory activity towards human protein tyrosine phosphatases PTP1B, LMW-PTP and TCPTP, enzymes which are involved in the development of insulin resistance. Compounds 5 and 8 showed from moderate to significant selectivity toward PTP1B over both the highly homologous TCPTP and the two isoforms of human LMW-PTP.
View Article and Find Full Text PDFNew 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells.
Eur J Med Chem
April 2012
Dipartimento Farmaco-chimico, University of Messina, Polo Universitario dell'Annunziata, Viale SS. Annunziata, 98168 Messina, Italy.
In pursuing our research targeting the identification of potent inhibitors of PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely related TC-PTP.
View Article and Find Full Text PDFSynthesis, activity and molecular modeling of a new series of chromones as low molecular weight protein tyrosine phosphatase inhibitors.
Bioorg Med Chem
April 2009
Department of Chemistry, University of Modena and R.E., Via G. Campi 183, 41100 Modena, Italy.
Protein tyrosine phosphatases (PTP) are crucial elements in eukaryotic signal transduction. Several reports suggested that the LMW-PTP family has oncogenic relevance. Moreover, LMW-PTP has been recognized as a negative regulator of insulin-mediated mitotic and metabolic signaling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!