Synthesis, neuroprotective and antioxidant capacity of PBN-related indanonitrones

Bioorg Chem. 2019 May:86:445-451. doi: 10.1016/j.bioorg.2019.01.071. Epub 2019 Feb 1.

Abstract

In this work six PBN-related indanonitrones 1-6 have been designed, synthesized, and their neuroprotection capacity tested in vitro, under OGD conditions, in SH-SY5Y human neuroblastoma cell cultures. As a result, we have identified indanonitrones 1, 3 and 4 (EC50 = 6.64 ± 0.28 μM) as the most neuroprotective agents, and in particular, among them, indanonitrone 4 was also the most potent and balanced nitrone, showing antioxidant activity in three experiments [LOX (100 μM), APPH (51%), DPPH (36.5%)], being clearly more potent antioxidant agent than nitrone PBN. Consequently, we have identified (Z)-5-hydroxy-N-methyl-2,3-dihydro-1H-inden-1-imine oxide (4) as a hit-molecule for further investigation.

Keywords: Antioxidant; Indanonitrones; Lipid peroxidation; Lipoxygenase inhibitors; Neuroprotection; PBN; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / antagonists & inhibitors
  • Amidines / pharmacology
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclic N-Oxides / chemistry
  • Cyclic N-Oxides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Indans / chemical synthesis
  • Indans / chemistry
  • Indans / pharmacology*
  • Lipid Peroxidation / drug effects
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Nitrogen Oxides / chemical synthesis
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / pharmacology*
  • Picrates / antagonists & inhibitors
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amidines
  • Antioxidants
  • Biphenyl Compounds
  • Cyclic N-Oxides
  • Indans
  • Neuroprotective Agents
  • Nitrogen Oxides
  • Picrates
  • nitrones
  • phenyl-N-tert-butylnitrone
  • 2,2'-azobis(2-amidinopropane)
  • 1,1-diphenyl-2-picrylhydrazyl
  • indan