Synthesis and biological evaluation of 3-carbamate smilagenin derivatives as potential neuroprotective agents

Bioorg Med Chem Lett. 2019 Oct 1;29(19):126622. doi: 10.1016/j.bmcl.2019.08.026. Epub 2019 Aug 13.

Abstract

Studies indicated that smilagenin, isolated from Anemarrhena asphodeloides Bunge, could improve cognitive impairment and exhibit neuroprotective activity. On the basis of the structure of smilagenin, a series of derivatives were synthesized and evaluated for their neuroprotective effects of H2O2-induced, oxygen glucose deprivation-induced neurotoxicity in SH-SY5Y cells and LPS-induced NO production in RAW264.7 cells. Structure activity relationship of derivatives revealed that benzyl-substituted piperazine formate derivatives showed the potent neuroprotective activity such as A12. These findings may provide new insights for the development of neuroprotective agents against Alzheimer's disease.

Keywords: Alzheimer’s disease; Neuroprotective activity; Oxidative stress; Smilagenin derivatives.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glucose / deficiency
  • Humans
  • Hydrogen Peroxide / toxicity
  • Mice
  • Molecular Structure
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism*
  • Oxidants / toxicity
  • Oxidative Stress / drug effects*
  • Oxygen / metabolism
  • RAW 264.7 Cells
  • Spirostans / chemistry*

Substances

  • Neuroprotective Agents
  • Oxidants
  • Spirostans
  • Nitric Oxide
  • Hydrogen Peroxide
  • sarsasapogenin
  • Glucose
  • Oxygen