Synthesis of N-arylpyridinium salts bearing a nitrone spin trap as potential mitochondria-targeted antioxidants.
The generation of excess reactive oxygen species (ROS) in mitochondria is responsible for much of the oxidative stress associated with ageing (aging), and mitochondrial dysfunction is part of the pathology of neurodegeneration and type 2 diabetes. Lipophilic pyridinium ions are known to accumulate in mitochondria and this paper describes a general route for the preparation of nitrone-containing N-arylpyridinium salts having a range of lipophilicities, as potential therapeutic antioxidants. The compatibility of nitrones with the Zincke reaction is the key to their synthesis. Their trapping of carbon-centred radicals and the EPR spectra of the resulting nitroxides are reported.
Robertson
Linsey
L
Centre for the Chemical Research of Ageing, WestCHEM Department of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.
Hartley
Richard C
RC
J Org Chem. 2007 Apr 27;72(9):3268-81
17391045
J Med Chem. 2006 May 4;49(9):2812-20
16640342
Cancer Res. 1996 Feb 1;56(3):538-43
8564968
Org Biomol Chem. 2006 Mar 7;4(5):896-901
16493474
Aging Cell. 2006 Feb;5(1):51-7
16441843
J Med Chem. 2007 Aug 23;50(17):3976-9
17649989
Free Radic Res. 2007 Jan;41(1):1-7
17164173
Chem Commun (Camb). 2007 Mar 14;(10):1083-5
17325813
Pharmazie. 1990 Sep;45(9):686-7
2284315
Nature. 2006 Oct 19;443(7113):787-95
17051205
J Med Chem. 2004 Apr 22;47(9):2337-47
15084132
J Chem Soc Perkin 1. 1966;23:2196-201
5951099
Bioorg Med Chem. 2007 May 15;15(10):3572-8
17379527
J Org Chem. 2007 Jul 20;72(15):5916-9
17590050
Annu Rev Pharmacol Toxicol. 2007;47:629-56
17014364
Antioxid Redox Signal. 2007 Oct;9(10):1757-71
17678441
Org Lett. 2003 Aug 7;5(16):2903-6
12889904
Bioorg Med Chem. 2003 Jan 17;11(2):281-91
12470721
Chem Biodivers. 2007 Sep;4(9):2253-67
17886845
Bioorg Med Chem. 2003 Jan 17;11(2):265-79
12470720
J Biochem Biophys Methods. 1996 Jul 10;32(3):183-90
8844325
Free Radic Biol Med. 1992;12(2):169-73
1313775
Org Lett. 2007 Aug 30;9(18):3499-502
17665918
Free Radic Biol Med. 2008 Apr 1;44(7):1394-405
18226602
Org Lett. 2006 Nov 23;8(24):5461-3
17107047
Bioorg Med Chem Lett. 2001 Mar 26;11(6):797-801
11277523
Angew Chem Int Ed Engl. 2006 Nov 27;45(46):7803-6
17072923
Bioorg Med Chem Lett. 2004 Feb 23;14(4):869-73
15012984
Arzneimittelforschung. 1967 May;17(5):605-7
5631589
Chemistry. 2007;13(33):9344-54
17729216
J Biol Chem. 2003 Dec 5;278(49):48534-45
12972420
Bioorg Med Chem Lett. 1998 Feb 17;8(4):379-84
9871689
Chem Res Toxicol. 2007 Jul;20(7):1053-60
17559235
J Biol Chem. 2005 Apr 22;280(16):16096-105
15722351
Biochem Biophys Res Commun. 2006 Aug 25;347(2):420-7
16828709
Arch Biochem Biophys. 2005 Mar 15;435(2):336-46
15708377
Circ Res. 2008 Feb 29;102(4):401-14
18309108