3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC(50) = 1.7 µmol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure-activity relationship indicated that the tricyclic scaffold and multi-bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC(50) of 0.89 µmol/L, which was approximately two-fold more potent than the initial lead compound BDB.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ardp.201100373 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Biomarkers.
Alzheimers Dement
December 2024
University of Fribourg, Adolphe Merkle Institute, Fribourg, Switzerland.
Background: Tau protein phosphorylation and aggregation are the pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. Multiple phosphorylation sites in Tau protein at serine (S), threonine (T), and tyrosine result in high heterogeneity and enhanced aggregation kinetics.
Method: Here, we used nanopores coated with a fluid lipid bilayer to characterize native and hyperphosphorylated Tau proteins on a single-molecule level.
Biomarkers.
Alzheimers Dement
December 2024
Douglas Mental Health Research Centre, Montreal, QC, Canada.
Background: Synaptic dysfunction is a central pathologic feature of Alzheimer's disease (AD), with synaptic loss even preceding neuronal loss in specific brain regions. In healthy individuals, synaptic function and plasticity are orchestrated through the complex integration of signaling inputs generated by cell surface receptors.
Methods: In this study, we investigate the role of one such receptor, protein tyrosine phosphatase receptor sigma (PTPRS), in the context of Alzheimer's disease.
Developing Topics.
Alzheimers Dement
December 2024
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Gothenburg, Sweden.
Background: Lewy bodies (LB), the main hallmark of Parkinson's disease (PD), are a frequent co-pathology in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The varying extents of LB pathology in these disorders can influence disease progression and severity. Consequently, understanding LB impact on the proteomic profile of these diseases is crucial, potentially leading to identifyng novel blood biomarkers related to this pathology which are urgently needed.
View Article and Find Full Text PDFBackground: DYRK1A overexpression, common in neurodegenerative diseases like Alzheimer's (AD), contributes to neurofibrillary tangles via Tau protein hyperphosphorylation and amyloid plaque formation, key AD hallmarks. Therefore, DYRK1A has been regarded as a novel target for neurodegenerative diseases. However, developing DYRK1A selective inhibitors has been a difficult challenge due to the highly conserved ATP-binding site of protein kinases, particularly among the CMGC family.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The TREAT-AD centers aim to improve Alzheimer's Disease (AD) research by offering free, high-quality tools and technologies. Lyn is a tyrosine kinase that belongs to the Src family kinases. The expression of Lyn and its activity have been implicated in AD.
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!