Carboplatin-containing porphyrin–platinum complexes as cytotoxic and phototoxic antitumor agents

Tetraarylporphyrins of the Ar:Ar′ = 3:1-type were synthesized from pyrrole, 4-hydroxybenzaldehyde and benzaldehydes substituted with ethyleneglycol, hydroxy and quaternary ammonium substituents for solubilization in DMF and, in particular, in water. After etherification with the tosylate of diethyl cyclobutanedicarboxylate and subsequent ester hydrolysis, the resulting carboxylic acid groups were used to bind platinum fragments bearing two ammonia and (RR/SS)-trans-1,2-diaminocyclohexane ligands, respectively, as non-leaving groups. In comparison to hematoporphyrin–platinum complexes, the title compounds show a 30 nm bathochromic shift of their absorption bands increasing the penetration depth of the red light used for irradiation in photodynamic tumor therapy. The antiproliferative activity of 24 new platinum complexes differing in the porphyrin ligands and the platinum fragments were studied in tests with J82 bladder cancer cells. The compounds showed the cytotoxic effect of the platinum moiety and after irradiation the phototoxic effect of the porphyrin system.