alpha-Aryl-N-alkyl Nitrones, as Potential Agents for Stroke Treatment: Synthesis, Theoretical Calculations, Antioxidant, Anti-inflammatory, Neuroprotective, and Brain-Blood Barrier Permeability Properties

作者：Chioua Mourad; Sucunza David; Soriano Elena; Hadjipavlou Litina Dimitra^*; Alcazar Alberto; Ayuso Irene; Jesus Oset Gasque Maria; Pilar Gonzalez Maria; Monjas Leticia; Isabel Rodriguez Franco Maria; Marco Contelles Jose; Samadi Abdelouahid

来源：Journal of Medicinal Chemistry, 2012, 55(1): 153-168.

DOI：10.1021/jm201105a

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)-alpha-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 is new lead compounds for further development in specific tests for potential stroke treatment.

• 出版日期2012-1-12