Villalonga-Barber, Carolina, Meligova, Aggeliki K, Alexi, Xanthippi, Steele, Barry R, Kouzinos, Constantinos E, Screttas, Constantinos G, Katsanou, Efrosini S, Micha-Screttas, Maria and Alexis, Michael N (2011) New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription. Bioorganic and Medicinal Chemistry, 19 (1). pp. 339-351. ISSN 0968-0896

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Abstract

We have synthesized a series of new (E) stilbenoid derivatives containing hydroxy groups at ring positions identical or similar to those of trans-resveratrol and bearing one or two bulky electron donating groups ortho to 4′-OH and we have evaluated their neuroprotective activity using glutamate-challenged HT22 hippocampal neurons to model oxidative stress-induced neuronal cell death. The most active derivatives, 5-{(E)-2-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]ethenyl}-1,3-benzenediol (2), 5-[(E)-2-(3,5-di-tert-butyl-4-hydroxyphenylethenyl)]-1,3-benzenediol (4) and 5-{(1E,3E)-4-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]-1,3-butadienyl}-1,3-benzenediol (6), had EC50 values of 30, 45 and 12 nM, respectively, and were ca. 100 to 400-fold more potent than resveratrol. Derivatives 2, 4 and 6 lacked cytotoxic activity against HT22 cells and estrogen receptor agonist or antagonist activity in estrogen response element-dependent gene expression and in estrogen-dependent proliferation of MCF-7 human breast cancer cells. In addition, they were incapable of interfering with aryl hydrocarbon receptor-mediated xenobiotic response element-dependent gene expression. Derivatives 2, 4 and 6 might assist in the development of lead candidates against oxidative stress-driven neurodegenerative diseases that will not increase endocrine cancer risk nor affect drug activation and detoxification mechanisms.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Chemistry
Depositing User:	Carolina Villalonga-Barber
Date Deposited:	16 Jun 2015 14:05
Last Modified:	28 Oct 2019 16:52
URI:	http://sro.sussex.ac.uk/id/eprint/54546

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