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

• Novel NCI8642 compounds were synthesized as potential LRP/DKK inhibitors.
• Novel inhibitors of LRPs/DKK1 interactions were identified.
• Important features for activity of NCI8642 template have been recognized.
• Gallocyanine dyes exhibit a sufficient physicochemical profile.
• NCI8642 and derivatives inhibit PGJ2-induced tau phosphorylation at serine 396.

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.

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