Synthesis and preliminary biological evaluations of ionic and nonionic amphiphilic alpha-phenyl-N-tert-butylnitrone derivatives.
In this study we report the synthesis of a series of new amphiphilic compounds derived from alpha-phenyl-N-tert-butylnitrone (PBN). The nitrone function was fitted into the core of the molecule between its polar and apolar groups. The polar head consisted of a lactobionamide, an ammonium, or a carboxylate group. The hydrophobic part consisted of a hydro- or a perfluorocarbon chain. The hydrophobic chain was linked to the tert-butyl group of the PBN derivatives using an urethane, a thioether, or an amide bond. The impact of these different parameters on the hydrophilic lipophilic balance of these compounds and their spin trap activity were studied. The various ESR measurements indicated that the aromatic and tert-butyl functional groups of PBN did not affect its spin trap properties. Moreover, these compounds were found to increase the viability of cultured human skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa mutation and presenting a severe ATPase deficiency.
Durand
Grégory
G
Laboratoire de Chimie BioOrganique et des Systèmes Moléculaire Vectoriels, Faculté des Sciences, 33 Rue Louis Pasteur, 84000 Avignon, France.
Polidori
Ange
A
Ouari
Olivier
O
Tordo
Paul
P
Geromel
Vanna
V
Rustin
Pierre
P
Pucci
Bernard
B
D000251:Adenosine Triphosphatases / Q000172:deficiency; D001259:Ataxia / Q000235:genetics; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D017240:Mitochondrial Myopathies / Q000235:genetics; D009154:Mutation; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics; D013329:Structure-Activity Relationship; D013577:Syndrome
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; C029217:phenyl-N-tert-butylnitrone; D000251:Adenosine Triphosphatases