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

Autor:	Taha F. S. Ali, Halil I. Ciftci, Mohamed O. Radwan, Eslam Roshdy, Ahmed M. Shawky, Mohammed A. S. Abourehab, Hiroshi Tateishi, Masami Otsuka, Mikako Fujita
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	azaindolin-2-one GSK3β Tau protein aggregation neurofibrillary tangles neuroprotective Medicine Pharmacy and materia medica RS1-441
Zdroj:	Pharmaceuticals, Vol 15, Iss 4, p 426 (2022)
Druh dokumentu:	article
ISSN:	1424-8247
DOI:	10.3390/ph15040426
Popis:	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 (E)-2f 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, (E)-2f was demonstrated to be non-toxic to normal cells, making it a promising neuroprotective lead compound that needs further investigation.
Databáze:	Directory of Open Access Journals
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