Synthesis, photophysical properties and photocytotoxicity of mono-, di-, tri- and tetra-glucosylated fluorophenylporphyrins

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 4; pp. 1526 - 1535
• Main Authors: Hirohara, Shiho, Nishida, Masataka, Sharyo, Kohei, Obata, Makoto, Ando, Tsuyoshi, Tanihara, Masao
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-02-2010; Elsevier
• Subjects: Biological and medical sciences; Cell Survival - drug effects; Cellular uptake; Chromatography, High Pressure Liquid; HeLa Cells; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Photochemistry; Photocytotoxicity; Photodynamic therapy (PDT); Photoradiation therapy and photosensitizing agent; Porphyrins - chemical synthesis; Porphyrins - chemistry; Porphyrins - pharmacology; Reactive oxygen species (ROS); S-Glucosylated porphyrin; Spectrophotometry, Ultraviolet; Treatment with physical agents; Treatment. General aspects; Tumors; Cellular uptake; Photocytotoxicity; Photodynamic therapy (PDT); S-Glucosylated porphyrin; Reactive oxygen species (ROS); Human; Oxidative stress; Photodynamic therapy; Cytotoxicity; Confocal microscopy; Uterine cervix; In vitro; Hela cell line; Biological activity; Uptake; Scanning microscope; Cell line; Thioglycoside; Phototoxicity; Fluorine Organic compounds; Chemical synthesis; Tumor cell; Porphyrin derivatives; Confocal laser scanning microscopy
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.01.006

We synthesized five possible perfluorophenylporphyrins having S-glucopyranosyl groups. The effect of the glycosylation patterns on the photocytotoxicity was discussed on the basis of photophysical properties as well as cellular uptake in HeLa cells.
In order to explore the effect of substitution patterns on the photocytotoxicity of glycoconjugated porphyrins, we synthesized and characterized a ‘complete set’ of tetrakis(perfluorophenyl)porphyrins having β-d-glucopyranosylthio groups on the phenyl ring. Among five possible derivatives, trans-substituted S-glucosylated porphyrin trans-2OH exerted outstanding photocytotoxicity (EC50 value was <5nM) in HeLa cells. The excellent photocytotoxicity of trans-2OH was found to be attributable to several factors, namely high optical transition probability in aqueous media, efficient type I photoreactions and enhanced cellular uptake.