Design and evaluation of Nrf2 activators with 1, 3, 4-oxa/thiadiazole core as neuro-protective agents against oxidative stress in PC-12 cells. Issue 2 (15th January 2020)

• Record Type: Journal Article
• Authors: Lin, Hongzhi; Qiao, Yuting; Yang, Hongyu; Li, Qi; Chen, Yao; Qu, Wei; Liu, Wenyuan; Feng, Feng; Sun, Haopeng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 2(2020)
• Publication Date: 2020-01-15
• Subjects: Nrf2 activator -- Neuro-protective agent -- Oxidative stress; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126853
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.