Thioflavones as novel neuroprotective agents

Ravishankar, D., Corona, G., Hogan, S. M., Spencer, J. P. E. ORCID: https://orcid.org/0000-0003-2931-7274, Greco, F. and Osborn, H. M. I. ORCID: https://orcid.org/0000-0002-0683-0457 (2016) Thioflavones as novel neuroprotective agents. Bioorganic & Medicinal Chemistry, 24 (21). pp. 5513-5520. ISSN 0968-0896 doi: 10.1016/j.bmc.2016.09.006

Abstract/Summary

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 (0.3 μM). 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-C=O moiety with a 4-C=S moiety also generally enhanced neuroprotection.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/66638
Identification Number/DOI	10.1016/j.bmc.2016.09.006
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > NMR (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Medicinal Chemistry Research Group Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	Elsevier
Download/View statistics	View download statistics for this item