Synthesis and in vitro anticancer activity of water-soluble cationic pyridylporphyrins and their metallocomplexes

Tetrapyrrolic compounds such as porphyrins are known to be prospective chemotherapeutics, and photosensitizers for cancer treatment and diagnosis. In this work, water-soluble, meso-substituted cationic pyridyl-porphyrins and their metallocomplexes bearing various central metal atoms (Ag, Zn, Co, and Fe) in the porphine ring and various functional groups (allyl, oxyethyl, butyl, and methallyl) at the nitrogen atom in the pyridine ring were synthesized and characterized by H-1 and C-13 NMR and UV-visible spectroscopy. Cytotoxic and photodynamic activities of new porphyrins and their metal derivatives were investigated in vitro (KCL-22 cancer cell line of human chronic myeloid leukemia). The cytotoxicity of porphyrins was shown to be dependent on the presence and type of the central metal atom in the porphine ring. Ag-derivatives were more cytotoxic than Co-, Zn-, and Fe-metallocomplexes. The porphyrins bearing allyl-functional groups were evidenced to be more cytotoxic than those which included butyl-, oxyethyl-, and methallyl-groups. The change of nitrogen position in the pyridine ring of Ag-metalloporphyrins from 3(3-N-pyridylporphyrins) to 4(4-N-pyridylporphyrins) induced an increase in the cytotoxic activity of metallocomplexes. All synthesized Ag-metalloporphyrins, except, the oxyethyl-containing one were more cytotoxic than cisplatin. Ally[ containing free porphyrin and its Zn-metallocomplex had higher phototoxicity than Ag-, Co-, and Fe-metalloporphyrins. The results obtained can be useful for further investigation of new porphyrins as potential chemotherapeutics and photosensitizers. Copyright (C) 2008 Society of Porphyrins & Phthalocyanines.