Abstract
Oxidative stress plays vital roles in virous neurodegenerative diseases including Alzheimer’s disease. Activation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), the key regulator of oxidative stress, may provide a new therapeutic strategy for these diseases. Herein we synthesized and evaluated a series of 1,3,4-oxa/thiadiazole core Nrf2 activators as neuroprotective agents. The representative compound 8 exhibited cytoprotective and Nrf2 activation effects in a neuron-like PC-12 cells. Additionally, compound 8 showed good membrane permeability, indicating this compound could penetrate blood–brain barrier (BBB) to reach central nervous system (CNS) as a neuro-protective agent. These results indicated that these Nrf2 activators with 1,3,4-oxa/thiadiazole core could serve as a new chemotype against oxidative stress in neurodegenerative diseases.
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