Methoxyphenyl Porphyrin Derivatives as Phototherapeutic Agents

M.      Elisa Milanesio; M.      Gabriela Alvarez; Edgardo      N. Durantini

doi:10.2174/157340710791184840

Abstract

Tetrapyrrolic macrocycles occupy a central place in bioorganic chemistry. On the basis of their photophysical properties, natural and synthetic porphyrin derivatives have found specific biomedical applications, particularly in the field of detection and treatment of neoplastic tissues. Photodynamic therapy (PDT) consists in the administration of a photosensitizer, which is selectively retained by the malign cells. The subsequent irradiation with visible light in the presence of oxygen specifically leads to cell death and tumor destruction. In the last years, methoxyphenyl porphyrin derivatives were evaluated as active phototherapeutic agents. Therefore, this review deals with the evolution of these photosensitizers with potential applications in PDT. The photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin was studied in different biomimetic and biological media. This synthetic porphyrin and its complexes with metals are effective photosensitizers, which were used as model compounds to investigate the theoretical and instrumental aspects of PDT. Modifications in the structure of methoxyphenyl porphyrins were performed to obtain an increase in the efficiency and selectivity of the agents. In these compounds, the presence of methoxy groups appears to be beneficial from the standpoint of tumor localization. Biochemical studies using a monocationic porphyrin showed efficient tumor regression and the cellular damage was mainly dependent on caspase-3 activity signaling response associated with apoptosis. Also, methoxyphenyl porphyrins attached to other structures, such as porphyrin and fullerene C60 were investigated as phototherapeutic drugs. In particular, porphyrin-C60 dyad was found to be an active compound, even under anoxic condition. The studies indicated that porphyrins bearing methoxy groups in the periphery of the macrocycle are interesting photosensitizers with potential application in photodynamic tumor therapy.

Keywords: Photodynamic therapy, cancer, tumor, photosensitizer, porphyrin, singlet oxygen