Photodynamic activity of monocationic and non-charged methoxyphenylporphyrin derivatives in homogeneous and biological media.
A novel 5-[4-(trimethylammonium)phenyl]-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide (2) has been synthesized. A positive charge was incorporated at a peripheral position to increase the amphiphilic character of the structure. The photodynamic effect of the cationic porphyrin 2 was compared with that of non-charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin (1), both in a homogeneous medium bearing photooxidizable substrates and in vitro on the Hep-2 human larynx carcinoma cell line. Absorption and fluorescence spectroscopic studies in different media show that 2 is essentially unaggregated in solution, and also in human cells. The singlet molecular oxygen, O2(1delta(g)), production was evaluated using 9,10-dimethylanthracene in N,N-dimethylformamide, yielding phi(delta) values of approximately 0.66 for both porphyrins. The addition of beta-carotene suppresses the O2(1delta(g))-mediated photooxidation. L-Tryptophan and guanosine 5'-monophosphate were used as biological substrate models. Porphyrin 2 sensitizes the decomposition of both compounds faster than does 1. In the biological medium, no dark cytotoxicity was observed, even though a high porphyrin concentration (10 microM) and a long incubation time (24 h) were employed. Cell treatments were performed with 5 microM of porphyrin for 24 h. Under these conditions, the uptake of porphyrin 2 into Hep-2 was about 3 times higher than that of 1. Cell survival after irradiation with visible light was dependent upon both the light exposure level and intracellular sensitizer concentration. Thus, a higher photocytotoxic effect was found for porphyrin 2 in comparison to 1. These results show that the amphiphilic monocationic porphyrin 2 could be a promising model for phototherapeutic agents with potential applications in tumor cell inactivation by photodynamic therapy.
Milanesio
M Elisa
ME
Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro 3, 5800 Río Cuarto, Córdoba, Argentina.
Alvarez
M Gabriela
MG
Silber
Juan J
JJ
Rivarola
Viviana
V
Durantini
Edgardo N
EN
D000873:Anthracenes / Q000737:chemistry; D002412:Cations; D006157:Guanosine Monophosphate / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000737:chemistry; D014407:Tumor Cells, Cultured; D019207:beta Carotene / Q000494:pharmacology
C481013:5-(4-(trimethylammonium)phenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin; D000873:Anthracenes; D002412:Cations; D011166:Porphyrins; D019207:beta Carotene; D006157:Guanosine Monophosphate; D014364:Tryptophan; C029126:9,10-dimethylanthracene