In-vitro activity and tissue distribution of new fluorinated meso-tetrahydroxyphenylporphyrin photosensitizers

Abstract

Abstract Tetra(hydroxyphenyl)porphyrins started to attract interest as potential photosensitizers for photodynamic therapy in the early eighties. Subsequently, a number of derivatives of these compounds have been studied. In 1997 we reported the synthesis of the fluorinated derivatives 5,10,15,20-tetrakis(2-fluoro-3-hydroxyphenyl)porphyrin (8), 5,10,15,20-tetrakis(2,4-difluoro-3-hydroxyphenyl)porphyrin (9), and 5,10,15,20-tetrakis(3,5-difluoro-4-hydroxyphenyl)porphyrin (10). We have measured their biological activity, using the MTT test, against cancer cell cultures in-vitro. The test showed that these compounds were as potent as 5,10,15,20-tetrakis(3-hydroxyphenyl)chlorin (5), one of the leading photosensitizers in photodynamic therapy. The highest photoactivity was shown by the meta-hydroxy compounds 8 and 9. The para-compound showed high toxicity in the dark. Distribution of these compounds between normal and cancer tissue was studied using 19F NMR spectroscopy. The highest cancer tissue localization was also shown by the meta-hydroxy compounds 8 and 9. The para compound showed poor localization in tumour tissue. This study has shown that 19F NMR spectroscopy can be used to estimate the tissue distribution of fluorinated tetrahydroxyphenylporphyrins in-vivo.