Synthesis and biological evaluation of 17beta-alkoxyestra-1,3, 5(10)-trienes as potential neuroprotectants against oxidative stress.
17beta-O-Alkyl ethers (methyl, ethyl, propyl, butyl, hexyl, and octyl) of estradiol were obtained from 3-O-benzyl-17beta-estradiol with sodium hydride/alkyl halide, followed by the removal of the O-benzyl protecting group via catalytic transfer hydrogenation. An increase compared to estradiol in the protection of neural (HT-22) cells against oxidative stress due to exposure of glutamate was furnished by higher (C-3 to C-8) alkyl ethers, while methyl and ethyl ethers decreased the neuroprotective effect significantly. Lipophilic (butyl and octyl) ethers blocking the phenolic hydroxyl (3-OH) of A-ring were inactive.
Prokai
L
L
Center for Drug Discovery, College of Pharmacy, Department of Anesthesiology, College of Medicine, and Center for Neurobiology of Aging, College of Pharmacy, University of Florida, Gainesville, Florida 32610-0497, USA. lprokai@grove.ufl.edu
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Prokai-Tatrai
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Abboud
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Simpkins
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D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D018696:Neuroprotective Agents; D004958:Estradiol