Neuroprotection by new ligustrazine-cinnamon acid derivatives on CoCl2-induced apoptosis in differentiated PC12 cells

Bioorg Chem. 2018 Apr:77:360-369. doi: 10.1016/j.bioorg.2018.01.029. Epub 2018 Feb 2.

Abstract

A new series of ligustrazine-cinnamon acid derivatives had been designed and synthesized as potential neuro-protective agents. Among the derivatives, 3a exhibited the promising neuroprotective activity (EC50 = 3.68 μM). Moreover, with the deep research of the drug pathway, it (the further mechanism researches) suggested compound 3a could inhibit the apoptosis of injured PC12 cells via blocking the mitochondria apoptosis pathway including up-regulation the ratio of Bcl-2/Bax, down-regulation the expression of cytochrome-c (Cyt-c) and inhibition of the activity of caspase-9 and -3. In addition, the structure-activity relationships (SARs) of novel compounds were also discussed.

Keywords: Apoptosis pathway; Ligustrazine-cinnamon acid derivatives; Neur-protective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Cobalt / pharmacology
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Pyrazines / chemistry
  • Pyrazines / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Cinnamates
  • Neuroprotective Agents
  • Pyrazines
  • cinnamic acid
  • Cobalt
  • cobaltous chloride
  • tetramethylpyrazine