Synthesis and Photophysical Properties of S-Mannosylated Chlorins and Their Effect on Photocytotoxicity in HeLa Cells

Abstract

5,10,15,20-Tetrakis(4-(α-D-mannopyranosylthio)-2,3,5,6-tetra-fluorophenyl)-2,3-(methano(N-methyl)iminomethano)chlorin (H2TFPC-SMan) has been prepared and characterized by1H and19FNMR and UV-vis spectroscopies, MALDI-TOF mass spectrometry, and elemental analysis. H2TFPC-SMan generates singlet oxygen (1O2) upon light irradiation. The value of the relative magnitude of the 1O2-generating ability of H2TFPC-SMan is comparable to that of 5,10,15,20-tetrakis(4-(β-D-glucopyranosylthio)-2,3,5,6-tetra-fluorophenyl)-2,3-(methano(N-methyl)iminomethano)chlorin (H2TFPC-SGlc). The dark and photocytotoxicity of H2TFPC-SMan and H2TFPC-SGlc were tested in HeLa cells. These compounds showed no cytotoxicity in the dark. Upon photo-irradiation, these compounds killed almost all of the cells in the region of a 1 to 2 ¯M concentration. The photocytotoxicity of the compounds completely disappeared in the concentration region of 0 to 0.1 ¯M. The photocytotoxicity of H2TFPC-SMan is significantly higher than that of H2TFPC-SGlc in the concentration range from 0.2 to less than 1 ¯M. The cellular uptake of H2TFPC-SMan in HeLa cells was estimated in terms of fluorescence intensity from each HeLa cell. The cellular uptake of H2TFPC-SMan is significantly higher than that of H2TFPC-SGlc at a concentration of 0.5 ¯M. These results are consistent with the experimental observation that the photocytotoxicity of H2TFPC-SMan is significantly higher than that of H2TFPC-SGlc in a concentration range from 0.2 to less than 1 ¯M.