engleski

Bioavailability of metalloporphyrin-based SOD mimics is greatly influenced by a single charge residing on a Mn site

In the cell Mn porphyrins(MnPs) likely couple with cellular reductans which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to 3 orders of magnitude depending upon length of alkylpyridyl chains and type of isomer. The effects result from the interplay of solvation, lipophilcity and stericity. Impact of ascorbate on accumulation of MnPs was measured in E. coli and in Balb/C mouse tumors 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 tumor than in surrounding muscle. Such data increase our understanding of MnPs cellular and subcellular 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.

SOD mimics; peroxynitrite scavengers; Mn(III) N-alkylpyridyl porphyrins

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