Design and synthesis of novel senkyunolide analogues as neuroprotective agents

Bioorg Med Chem Lett. 2018 Feb 15;28(4):668-672. doi: 10.1016/j.bmcl.2018.01.018. Epub 2018 Jan 12.

Abstract

A class of senkyunolide analogues bearing benzofuranone fragment were designed, synthesized and evaluated for their neuroprotective effect in models of oxygen glucose deprivation (OGD) and oxidative stress. All tested compounds showed neuroprotection profile based on the cell viability assay. In particular, derivatives 1f-1i possessing furoxan-based nitric oxide releasing functionality exhibited significant biological activities in OGD models. More importantly, compound 1g containing short linker with furoxan displayed the most potent neuroprotection at the concentration of 100 μM (cell survival up to 145.2%). Besides, 1g also showed the middle level neuroprotective effect in model of oxidative stress.

Keywords: Acute cerebral ischemia; Furoxan; Neuroprotective agents; Senkyunolide analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / pharmacology
  • Benzofurans / chemical synthesis
  • Benzofurans / pharmacology*
  • Cell Line
  • Coumaric Acids / pharmacology
  • Drug Design
  • Mice
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Donors / chemical synthesis
  • Nitric Oxide Donors / pharmacology*
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / pharmacology*
  • Oxidative Stress / drug effects

Substances

  • Antioxidants
  • Benzofurans
  • Coumaric Acids
  • Neuroprotective Agents
  • Nitric Oxide Donors
  • Oxadiazoles
  • 3-N-butyl-4,5-dihydrophthalide
  • ferulic acid