Porphyrin chemistry pertaining to the design of anti-cancer drugs; part 2, the synthesis and in vitro tests of water-soluble porphyrins containing, in the meso positions, the functional groups: 4-methylpyridinium, or 4-sulfonatophenyl, in combination with phenyl, 4-pyridyl, 4-nitrophenyl, or 4-aminophenyl

Abstract

Water-soluble, meso-substituted porphyrins are synthesized by sulfonation or methylation of the phenyl or pyridyl groups, respectively, of some non-water-soluble functionalized porphyrins that we have recently synthesized (Can. J. Chem. 72, 1894 (1994)). Twelve anionic sulfonated and seven cationic methylpyridinium porphyrins, usually containing other functional groups (phenyl, pyridyl, nitro- and amino-phenyl), are reported on. Twelve of these porphyrins are new, and all nineteen porphyrins are characterized by 1H NMR. UV–VIS data are presented for the isolated porphyrins, while mass spectral data are noted for selected compounds. Partition coefficients of the porphyrins in octanol–water, and the accumulation of the porphyrins in HT-29 cells of a human-cancer tumor, were measured and both were inversely related to the charges of the porphyrins. The 11 porphyrins soluble in biological buffer solutions are basically nontoxic to Chinese hamster ovary (CHO) cells in oxic or hypoxic conditions or to aerobic HT-29 cells at the 100 µM concentration used (which is sometimes limited by solubility). No significant X-ray radiosensitization was observed for selected porphyrins toward CHO cells at the 100 µM concentrations used, but some photosensitized cell kill (using 630 nm light) was observed using the disodium salt of 5,10-bis(4-pyridyl)-15,20-bis(4-sulfonatophenyl)porphyrin (24).