Project/Area Number |
09556022
|
Research Category |
Grant-in-Aid for Scientific Research (B).
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Bioproduction chemistry/Bioorganic chemistry
|
Research Institution | Mie University |
Principal Investigator |
KASHIMURA Naoki Mie University, Faculty of Bioresources, Professor, 生物資源学部, 教授 (20026412)
|
Co-Investigator(Kenkyū-buntansha) |
SAIKI Ikuo Toyama Medical and Pharmaceutical University, Institute of Oriental Medicine, Professor, 和漢薬研究所, 教授 (80133776)
INAGAKI Minoru Mie University, Faculty of Bioresources, Assistant Professor, 生物資源学部, 助手 (20242935)
YOSHIDA Toshimichi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80166959)
TANIMOTO Toshiko Mukogawa Wemen's University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (10151870)
KIOKA Noriyuki Kyoto University, Faculty of Agriculture, Assistant Professor, 農学部, 助手 (90234179)
坂倉 照〓 (坂倉 照よ) 三重大学, 医学部, 教授 (80073120)
|
Project Period (FY) |
1997 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥5,600,000 (Direct Cost: ¥5,600,000)
|
Keywords | lipophilic sugars / antimetstatic activities / human cancer cell lines / antiadhesive action / partially benzylated sugars / purine derivatives / 細胞接着阻害 / がん転移阻害 / 抗炎症活性 / 部分置換糖質 / ヒトがん細胞 / マウス乳がん細胞 / 脂溶性糖質誘導体 / がん転移自然モデル / がん転移血行モデル / 細胞毒性 / トリチルヌクレオシド / トリチルシクロデキストリン / がん転移 / 血管内皮細胞 / 接着分子 / がん細胞浸潤 / トリチル化糖 |
Research Abstract |
This project aimed to focus on the anti-metastatic action of lipophilic sugar derivatives, to make molecular design, and to find out novel lead compounds for new anti-cancer drugs, based on the previous studies on the anti-adhesive sugar derivatives. Of 500 compounds investigated, 8 derivatives were finally selected to subject to a series of in vitro and in vivo tests. Partially benzylated sugars were found to be one of the best compounds for the cadidate of new lead compounds, because of their easy availability of both various isomers and materials, nontoxicity, and effective action in in vivo tests. Especially those available from biomass such as chitin, fucoidan, and xylan, are of interest for future development. Various purine derivatives were studied on their anti-tumor activities. Several ethynylpurine derivatives were found to exhibit specific inhibitory action against the expression of adhesion molecules of human endothelial cells. It was further found that 4 compounds exhibit strong anti-growth action against more than 30 human cancer cell lines with at the concentration of less than 10^<-6>M.One of them was found to be effective in vivo.The main features of the present study include expected new mechanism, low toxicity and availability from biomass at low cost.
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