Synthesis and in vitro photodynamic activities of water-soluble fluorinated tetrapyridylporphyrins as tumor photosensitizers

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 10; pp. 2789 - 2794
• Main Authors: Ko, Yoon-Joo, Yun, Kyung-Jin, Kang, Min-Seok, Park, Jongmin, Lee, Kyung-Tae, Park, Seung Bum, Shin, Jung-Hyu
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.05.2007; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Fluorinated tetrapyridylporphyrins; Fluorine - chemistry; HeLa Cells; Humans; Medical sciences; Photochemistry; Photochemotherapy; Photocytotoxicity; Photodynamic therapy (PDT); Photoradiation therapy and photosensitizing agent; Photosensitizer; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - pharmacology; Porphyrins - chemical synthesis; Porphyrins - therapeutic use; Reactive oxygen species (ROS); Solubility; Treatment with physical agents; Treatment. General aspects; Tumors; Water - chemistry; Photocytotoxicity; Photodynamic therapy (PDT); Photosensitizer; Reactive oxygen species (ROS); Fluorinated tetrapyridylporphyrins; Flow cytometry; Oxidative stress; Organic cation; Cytotoxicity; Uterine cervix; MTT assay; Pyridinium compounds; Structure activity relation; Mechanism of action; Chemical synthesis; Human; Photodynamic therapy; Iminium compounds; In vitro; Hela cell line; Water soluble compound; Cell line; Organic fluorine compounds; Phototoxicity; Photochemical stability; Porphyrin derivatives; Apoptosis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.02.083

A series of water-soluble fluoro-substituted porphyrins were synthesized, and photocytotoxicity studies of these compounds evaluated by MTT assay on HeLa cells in vitro. A series of water-soluble fluorinated cationic porphyrins were designed, synthesized, and characterized. In vitro photocytotoxicity of these compounds was evaluated by MTT assay on HeLa cells. Their photocytotoxicity was dependent on the positions of the cations and the fluorines in the pyridine ring, and 5,10,15,20-tetrakis-( N-methyl-2-fluoro-pyridin-3-yl)-porphyrin ( 8) showed the most potent photo-induced cytotoxicity without photobleaching. PDT-induced ROS inside HeLa cells was measured with flow cytometry using ROS-sensitive fluorometric probe, 2,7-dichlorofluororescin (DCF), which revealed high correlations of ROS with cellular cytotoxicity. FACS analysis shows that PDT with porphyrin 8 induced apoptosis in HeLa cells. In summary, efficient generation of ROS, biological effectiveness, and good photostability of porphyrin 8 indicate its potential application in photodynamic therapy (PDT) in the near future.