Μίχα-Σκρέττα, ΜαρίαΣκρέττας, Κωνσταντίνος Γ.Βιλλιαλονγκα-Μπαρμπέρ, ΚαρολίναMeligova, Aggeliki K.Kouzinos, Constantinos E.Alexi, XanthippiΣτηλ, ΜπάρυΑλέξης, Μιχαήλ Ν.Katsanou, Efrosini S.OXFORDWe 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 EC(50) 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.Adobe PDF339-35110.1016/j.bmc.2010.11.018https://hdl.handle.net/10442/123080968-0896engPergamon© 2010 Elsevier Ltd. All rights reserved.© 2010 Elsevier Ltd. All rights reserved.Bioorganic & Medicinal ChemistryOxidative stressEstrogen receptorArylhydrocarbon receptorNeuronal damageStilbenoid derivativesChemistry, MedicinalNew hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcriptionΆρθρο σε επιστημονικό περιοδικό2011-01-01Δημοσίευση σε περιοδικόPublication in journalΟργανική χημείαOrganic Chemistryisi - Chemistry, Organic includes resources that focus on synthetic and natural organic compounds their synthesis, structure, properties, and reactivity. Research on hydrocarbons, a major area of organic chemistry, is included in this category.Φαρμακευτική χημείαMedicinal chemistryisi - Chemistry, Medicinal includes resources emphasizing the isolation and study of substances with therapeutic potential. Topics of interest are quantitative structure-function relationships, structural characterization and organic syntheses of naturally occurring compounds, and chemical and analytical techniques used in rational drug design. See also the PHARMACOLOGY & PHARMACY category.Φαρμακολογία και ΦαρμακευτικήPharmacology and Pharmacyisi - Pharmacology & Pharmacy covers resources on the discovery and testing of bioactive substances, including animal research, clinical experience, delivery systems, and dispensing of drugs. This category also includes resources on the biochemistry, metabolism, and toxic or adverse effects of drugs.ΒιολογίαBiological sciencesFrascati 42Επιστημονικό άρθροScientific articleΕθνικό Ίδρυμα Ερευνών (ΕΙΕ)Greek Aggregator OpenArchives.gr | National Documentation Centre (EKT)