Synthesis of methoxy-X04 derivatives and their evaluation in Alzheimer's disease pathology.

Abstract

BACKGROUND:

Alzheimer's disease is characterized by two notorious protein aggregates in the brain: extracellular senile plaques mainly consisting of amyloid-β peptides and tau-protein-derived intracellular paired helical filaments. The diagnosis of Alzheimer's disease is impaired by insufficient sensitivity and specificity of diagnostic methods to visualize these pathological hallmarks over all disease stages.

OBJECTIVE:

The established fluorescence marker methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with good specificity, yet it is limited by slow elimination in vivo. Since the need for new markers is high, we prepared methoxy-X04 derivatives and evaluated their potential as imaging agents in Alzheimer's disease pathology.

METHODS AND RESULTS:

In this study, we describe an improved synthesis for methoxy-X04 and its derivatives and their affinity determination for the respective protein targets by immunohistology and a displacement assay.

CONCLUSION:

This resulted in the identification of new derivatives of methoxy-X04 with improved binding affinity.

• Authors: Alexander Boländer, Daniel Kieser, Christoph Scholz, Roland Heyny-von Haußen, Gerhard Mall, Valérie Goetschy, Christian Czech, Boris Schmidt
• Journal: Neuro-degenerative diseases (Neurodegener Dis) Vol. 13 Issue 4 Pg. 209-13 ( 2014) ISSN: 1660-2862 [Electronic] Switzerland
• PMID: 24080522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,4-bis(4'-hydroxystyryl)-2-methoxybenzene
• Alkenes
• Benzene Derivatives
• Stilbenes

Topics

• Alkenes (chemical synthesis)
• Alzheimer Disease (pathology)
• Benzene Derivatives (chemical synthesis)
• Humans
• Stilbenes