Synthesis and evaluation of gallocyanine dyes as potential agents for the treatment of Alzheimer's disease and related neurodegenerative tauopathies

Spyros Mpousis; Savvas Thysiadis; Nicolaos Avramidis; Sotirios Katsamakas; Spiros Efthimiopoulos; Vasiliki Sarli

doi:10.1016/j.ejmech.2015.11.024

Synthesis and evaluation of gallocyanine dyes as potential agents for the treatment of Alzheimer's disease and related neurodegenerative tauopathies

Eur J Med Chem. 2016 Jan 27:108:28-38. doi: 10.1016/j.ejmech.2015.11.024. Epub 2015 Nov 22.

Authors

Spyros Mpousis¹, Savvas Thysiadis¹, Nicolaos Avramidis², Sotirios Katsamakas³, Spiros Efthimiopoulos⁴, Vasiliki Sarli⁵

Affiliations

¹ Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece.
² Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia, Greece.
³ Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece.
⁴ Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia, Greece. Electronic address: efthis@biol.uoa.gr.
⁵ Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece. Electronic address: sarli@chem.auth.gr.

PMID: 26629858
DOI: 10.1016/j.ejmech.2015.11.024

Abstract

In search of safe and effective anti-Alzheimer disease agents a series of gallocyanine dyes have been synthesized and evaluated for their ability to inhibit LRPs/DKK1 interactions. Modulation of the interactions between LRPS and DKK1, regulate Wnt signaling pathway and affect Tau phosphorylation. The current efforts resulted in the identification of potent DKK1 inhibitors which are able to inhibit prostaglandin J2-induced tau phosphorylation at serine 396.

Keywords: Alzheimer's disease; DKK1 inhibitors; DKK1/LRP6 interaction inhibitors; Gallocyanine; Phenoxazine; Tau phosphorylation inhibition; Tauopathies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Coloring Agents / chemical synthesis
Coloring Agents / chemistry
Coloring Agents / therapeutic use*
Dose-Response Relationship, Drug
Humans
Intercellular Signaling Peptides and Proteins / metabolism
Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
Models, Molecular
Molecular Structure
Oxazines / chemical synthesis*
Oxazines / chemistry
Oxazines / therapeutic use*
Phosphorylation / drug effects
Protein Binding / drug effects
Structure-Activity Relationship
Tauopathies / drug therapy*
tau Proteins / metabolism

Substances

Coloring Agents
DKK1 protein, human
Intercellular Signaling Peptides and Proteins
Low Density Lipoprotein Receptor-Related Protein-1
Oxazines
tau Proteins
gallocyanine