Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia
Walker, James R , Fairfull-Smith, Kathryn E., Anzai, Kazunori , Lau, Shannen , White, Paul J , Scammells , Peter J. , & Bottle , Steven E. (2011) Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia. MedChemComm, pp. 436-441.
A novel antioxidant for the potential treatment of ischaemia was designed by incorporating an isoindoline nitroxide into the framework of the free radical scavenger edaravone. 5-(3-Methyl-pyrazol-5-ol-1-yl)-1,1,3,3-tetramethylisoindolin-2-yloxyl 7 was prepared by N-arylation of 3-methyl-5-pyrazolone with 5-iodo-1,1,3,3-tetramethylisoindoline-2-yloxyl 8 in the presence of catalytic copper(I)iodide. Evaluation of 7, its methoxyamine derivative 10 and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) against edaravone 1 in ischaemic rat atrial cardiomyocytes revealed significant decreases in cell death after prolonged ischaemia for each agent; however the protective effect of the novel antioxidant 7 (showing greater than 85% reduction in cell death at 100 μM) was significantly enhanced over that of edaravone 1 alone. Furthermore, the activity for 7 was found to be equal to or greater than the potent cardioprotective agent N6-cyclopentyladenosine (CPA). The methoxyamine adduct 10 and edaravone 1 showed no difference between the extent of reduction in cell death whilst CTMIO had only a modest protective effect.
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|Item Type:||Journal Article|
|Keywords:||cardiovascular ischaemia, Edaravone , isoindoline nitroxides|
|Divisions:||Past > Schools > Chemistry|
Past > QUT Faculties & Divisions > Faculty of Science and Technology
|Copyright Owner:||Copyright 2011 Royal Society of Chemistry|
|Deposited On:||27 Jul 2011 14:17|
|Last Modified:||28 Jul 2011 15:23|
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