Synthesis and biological evaluation of methoxyphenyl porphyrin derivatives as potential photodynamic agents.

A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro-4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was found for 6, which has higher singlet molecular oxygen, O(2)((1)Delta(g)), production.

Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: photochemical characterization and biological consequences in a human carcinoma cell line.

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of 0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was used as biological substrate to analyze the O2(1 delta g)-mediated photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were proportional to the sensitizer quantum yield of O2(1 delta g). A value of approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the cells exposed to visible light. The cell survival at different light exposure levels was dependent on phi delta. Under these conditions, the cytotoxic effect increases in the order: Cu-TMP << TMP < ZnTMP approximately CdTMP, correlating with the production of O2(1 delta g). A similar behavior was observed in both the chemical and biological media indicating that the O2(1 delta g) mediation appears to be mainly responsible for the cell inactivation.