Potency and Selective Toxicity of Tetra(hydroxyphenyl)‐ and Tetrakis(dihydroxyphenyl)porphyrins in Human Melanoma Cells, With and Without Exposure to Red Light

Abstract

A series of tetra(hydroxyphenyl)-(2-, 3- and 4-hydroxy; THPP) and tetrakis(dihydroxyphenyl)porphyrins (2,3-, 2,4-, 2,5-, 3,4-, and 3.5-dihydroxy; TDHPP) was synthesized and tested for toxicity in HeLa cells and human melanoma cell lines. Irradiation of drug-treated cells with > 600 nm light greatly increased the toxicity of all drugs except the 2,5- and 3,5-TDHPP. The THPP were more toxic than TDHPP in all cell lines, with or without irradiation; of the dihydroxy derivatives, the 3,4- and 2,4-isomers were the most toxic and the 2,5-isomer was the least toxic. The MM96E melanoma cell line, shown previously to be sensitive to hydrogen peroxide and superoxide ion, was not hypersensitive to killing by any of the above agents. HeLa cells, which lacked glutathione-S-transferase activity, were sensitive to the 4- and 2,3-isomers after irradiation; similar amounts of all drugs were taken up by HeLa cells. The pigmented melanoma cell line MM418, resistant to UV-B and in situ-generated hydrogen peroxide but sensitive to glutathione (GSH) depletion, was found to be resistant to the 2,3-isomer (no irradiation) and sensitive to the 3,4-isomer. The results indicate that (1) phototoxicity in these phenylporphyrins is not mediated by superoxide ions or hydroxyl radicals, (2) toxicity is dependent on the orientation of the hydroxy groups, (3) GSH transferase and possibly GSH itself offer protection from the 4- and 3,4-derivatives, respectively, and (4) the 3,4-derivative and analogues of similar selectivity should be evaluated further for the treatment of primary melanoma.

Spectral investigations of the interaction of some porphyrins with bovine serum albumin

“…In addition, T4CPP, meso-tetrakis [3-(carboxymethyleneoxy)phenyl]porphyrin (T3CPP) and T3, 4BCPP have been shown to photocleave plasmid DNA, and the photocleavage of DNA is more for T3CPP than for T4CPP and T3, 4BCPP [31,32]. Their parent porphyrins meso-tetrakis(4-hydroxyphenyl)porphyrin (T4HPP), meso-tetrakis(3-hydroxyphenyl)porphyrin (T3HPP) and meso-tetrakis (3,4-dihydroxyphenyl)porphyrin (T3, 4DHPP) show increased tumour photonecrosis in comparison with haematoporphyrin derivative, and this tumour necrosis is more for T3HPP than for T4HPP [13,33,34]. Recently, meso-tetrakis [3-(carboxymethylene)phenyl]chlorin (T3CPC), a chlorin analogue of T3CPP, has been found to destroy ovarian tumours in the presence of light and molecular oxygen, and it has negligible dark toxicity [35].…”

Photosensitized singlet oxygen and its applications

“…meso -Tetraphenylporphyrins are synthetically accessible and can be easily substituted in the phenyl group to add to the hydrophilicity. Unfortunately, the ortho hydroxy phenyl isomer causes skin sensitivity, but the meta and para isomers show improved tumor phototoxicity and selectivity over haematoporphryin derivative [33,65]. The methyl pyridinium salt causes significant tumor photodamage, attributed to the increase in hydrophilicity imparted by the cationic substituent [66].…”

Design and Synthesis of a Multi Cu(II)-porphyrin Array

“…The porphyrin core 1 and 4 were obtained from para-hydroxybenzaldehyde, benzaldehyde and pyrrole by the conventional method [24,25]. The tetrahydroxyporphyrin was used as free based material.…”