Aza-CGP37157-lipoic hybrids designed as novel Nrf2-inducers and antioxidants exert neuroprotection against oxidative stress and show neuroinflammation inhibitory properties

Drug Dev Res. 2020 May;81(3):283-294. doi: 10.1002/ddr.21618. Epub 2019 Nov 6.

Abstract

Two multitarget hybrids, derived from an aza-analogue of CGP37157, a mitochondrial Na+ /Ca2+ exchanger antagonist, and lipoic acid were designed in order to combine in a single molecule the antioxidant and Nrf2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The hybrid derivatives showed Nrf2 induction and radical scavenging properties, leading to a good neuroprotective profile against oxidative stress, together with an interesting antineuroinflammatory activity. The results obtained show differences in activity depending on the configuration of the chiral center of LA.

Keywords: Nrf2 induction; anti-inflammatory activity; neuroprotection; radical scavenging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Line
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Thiazepines / chemistry
  • Thiazepines / pharmacology*
  • Thioctic Acid / chemistry
  • Thioctic Acid / pharmacology*

Substances

  • 7-chloro-5-(2-isopropylphenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one
  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neuroprotective Agents
  • Thiazepines
  • Thioctic Acid