2004 Fiscal Year Final Research Report Summary
Design of hypoxic cell radiosensitizer utilized for hypoxia orientation of macrophage
| Project/Area Number |
14370758
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HORI Hitoshi The University of Tokushima, Department of Biological Science & Technology, Professor, 工学部, 教授 (90119008)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAWA Hideko The University of Tokushima, Department of Biological Science & Technology, Associate Professor, 工学部, 助教授 (90207994)
UTO Yoshihiro The University of Tokushima, Department of Biological Science & Technology, Assistant Professor, 工学部, 助手 (20304553)
SOMA Genichiro Tokushima Bunri University, Institute for Health Sciences, Professor, 健康科学研究所, 教授 (00158990)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Hypoxic Cell Radiosensitizer / Macrophage / Hypoxia Orientation / TX-2068 / TX-1877 / N-Acetylgalactosamine |
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| Research Abstract |
We designed a novel hypoxic cell radiosensitizer TX-2068 that utilize for hypoxia orientation of macrophage. TX-2068 has a N-acetylgalactosamine moiety as a macrophage recognition group and TX-1877 moiety as a radiosensitizing group. We synthesized TX-2068 at condensation reaction with acetylated N-acetylgalactosamine and TX-1877 using BF3 as a catalyst followed by deprotection of O-acetyl group, TX-2068 was obtained by the total yield 35%. Water-octanol distribution coefficient (Poct) of TX-2068 was Poct = 0.0010, and a very high water solubility was shown compared with Poct = 0.056 of TX-1877. Radiosensitizing activity of TX-2068 was indicated as a enhancement ratio (ER) = 1.88 (1 mM) with EMT6/KU cell, and a little high sensitization revitalization was shown compared with ER = 1.75 (1 mM) of TX-1877. The degree of macrophage activation of TX-2068 was evaluated by macrophage phagocytic activation experiment. As a result, phagocytic activity was increased by the use of TX-2068 up to 1 mM and decreased at 5 mM. We suggested that this behavior is the bell-sharp type activation curve as a generally seen in immune reaction, and TX-2068 be activated of the macrophage. Besides, cytotoxicity for the macrophage cell of TX-2068 was not observed up to 5 mM at MTT method. From the all above-mentioned results, we concluded that TX-2068 is a bifunctional drug having radiosensitizing activity and macrophage phagocytic activity without cytotoxicity. Finally we finish the scientific research titled "Design of hypoxic cell radiosensitizer utilized for hypoxia orientation of macrophage".
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