Discovery of Azaindolin-2-One as a Dual Inhibitor of GSK3β and Tau Aggregation with Potential Neuroprotective Activity

• Main Authors: Taha F. S. Ali (Author), Halil I. Ciftci (Author), Mohamed O. Radwan (Author), Eslam Roshdy (Author), Ahmed M. Shawky (Author), Mohammed A. S. Abourehab (Author), Hiroshi Tateishi (Author), Masami Otsuka (Author), Mikako Fujita (Author)
• Format: Book
• Published: MDPI AG, 2022-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

The inhibition of glycogen synthase kinase 3β (GSK3β) activity through pharmacological intervention represents a promising approach for treating challenging neurodegenerative disorders like Alzheimer's disease. Similarly, abnormal tau aggregate accumulation in neurons is a hallmark of various neurodegenerative diseases. We introduced new dual GSK3β/tau aggregation inhibitors due to the excellent clinical outcome of multitarget drugs. Compound <b>(<i>E</i>)-2f</b> stands out among the synthesized inhibitors as a promising GSK3β inhibitor (IC₅₀ 1.7 µM) with a pronounced tau anti-aggregation effect in a cell-based model of tauopathy. Concurrently, <b>(<i>E</i>)-2f</b> was demonstrated to be non-toxic to normal cells, making it a promising neuroprotective lead compound that needs further investigation.

Item Description

10.3390/ph15040426
1424-8247