α-aryl-N-alkyl nitrones, as potential agents for stroke treatment: Synthesis, theoretical calculations, antioxidant, anti-inflammatory, neuroprotective, and brain-blood barrier permeability properties

Mourad Chioua, David Sucunza, Elena Soriano, Dimitra Hadjipavlou-Litina, Alberto Alcázar, Irene Ayuso, María Jesús Oset-Gasque, María Pilar González, Leticia Monjas, María Isabel Rodríguez-Franco, José Marco-Contelles, Abdelouahid Samadi

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

We report the synthesis, theoretical calculations, the antioxidant, anti-inflammatory, and neuroprotective properties, and the ability to cross the blood-brain barrier (BBB) of (Z)-α-aryl and heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority of nitrones compete with DMSO for hydroxyl radicals, and most of them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that nitrones 1-3 and 10 give rise to significant neuroprotection. When compounds 1-11 were tested for necrotic cell death (LDH release test) nitrones 1-3, 6, 7, and 9 proved to be neuroprotective agents. In vitro evaluation of the BBB penetration of selected nitrones 1, 2, 10, and 11 using the PAMPA-BBB assay showed that all of them cross the BBB. Permeable quinoline nitrones 2 and 3 show potent combined antioxidant and neuroprotective properties and, therefore, can be considered as new lead compounds for further development in specific tests for potential stroke treatment.

Original languageEnglish
Pages (from-to)153-168
Number of pages16
JournalJournal of Medicinal Chemistry
Volume55
Issue number1
DOIs
Publication statusPublished - Jan 12 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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