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ID: ALA3860078

Journal: Bioorg Med Chem

Title: Thioflavones as novel neuroprotective agents.

Authors: Ravishankar D, Corona G, Hogan SM, Spencer JPE, Greco F, Osborn HMI.

Abstract: Oxidative stress is associated with the pathology of neurodegenerative diseases. Identification of small molecules capable of protecting against oxidative stress is therefore of significant importance. In this context, a library of 76 hydroxy flavones, methoxy flavones and their 4-thio analogues has been evaluated for neuroprotection against H2O2-induced oxidative stress. This revealed the synthetic 7,8-dihydroxy 4-thioflavones as neuroprotective compounds, with 14d and 18d showing highest neuroprotective effects at lower concentrations (0.3μM). Neuroprotection was found to be mediated via activation of the anti-apoptotic cell survival proteins of the ERK1/2 and PI3K/Akt pathways. Structure-activity relationship analysis revealed the B-ring phenyl group as essential for greater neuroprotection. Replacing the 4-CO moiety with a 4-CS moiety also generally enhanced neuroprotection.

CiteXplore: 27663547

DOI: 10.1016/j.bmc.2016.09.006