Synthesis and biological evaluation of 17beta-alkoxyestra-1,3, 5(10)-trienes as potential neuroprotectants against oxidative stress

J Med Chem. 2001 Jan 4;44(1):110-4. doi: 10.1021/jm000280t.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzyl Compounds / chemical synthesis*
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Estradiol / analogs & derivatives*
  • Estradiol / chemical synthesis*
  • Estradiol / chemistry
  • Estradiol / pharmacology
  • Mice
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects*
  • Structure-Activity Relationship

Substances

  • Benzyl Compounds
  • Neuroprotective Agents
  • Estradiol