期刊
FREE RADICAL RESEARCH
卷 45, 期 2, 页码 188-200出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10715762.2010.522575
关键词
SOD mimics; peroxynitrite scavengers; Mn(III) N-alkylpyridyl porphyrins
资金
- Wallace H. Coulter Translational Partners
- National Institutes for Allergy and Infectious Diseases [U19AI0677989]
- NIH/NCI Duke Comprehensive Cancer Center [5-P30-CA14236-29]
- Kuwait University [U19AI0677989, MB03/07, R01 CA098452]
- Hefei National Laboratory for Physical Sciences at the Microscale at University of Science and Technology of China
In the cell Mn porphyrins (MnPs) likely couple with cellular reductants which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to three orders of magnitude depending upon the length of alkylpyridyl chains and type of isomer. The effects result from the interplay of solvation, lipophilicity and stericity. Impact of ascorbate on accumulation of MnPs was measured in E. coli and in Balb/C mouse tumours and muscle; for the latter measurements, the LC/ESI-MS/MS method was developed. Accumulation was significantly enhanced when MnPs were co-administered with ascorbate in both prokaryotic and eukaryotic systems. Further, MnTnHex-2-PyP5+ accumulates 5-fold more in the tumour than in a muscle. Such data increase our understanding of MnPs cellular and sub-cellular accumulation and remarkable in vivo effects. The work is in progress to understand how coupling of MnPs with ascorbate affects their mechanism of action, in particular with respect to cancer therapy.
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