A Novel Synthesis of Molecular-Targetting Indole Alkaloids and Elucidation of Anticancer Mechanism by Inducing Apoptosis
| Project/Area Number |
24590025
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Norio 東京理科大学, 理工学部, 准教授 (00328569)
IKEDA Reiko 東京理科大学, 理工学部, 助教 (60516441)
AOKI Shin 東京理科大学, 薬学部, 教授 (00222472)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 抗がん剤 / β-カルボリン / エリプチシン / ピリジン / ピリミジン / アポトーシス / ヘテロ環合成 / フルオラス合成 / logP / 合成 / ヘテロ環 / ピリドピリミジン / PEGエステル / チューブリン重合阻害 / 配糖体 |
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| Outline of Final Research Achievements |
First, we have synthesized a series of new β-carboline derivatives, and evaluated their antitumor activity against HeLa S-3 cells to clarify its action mechanism and to provide its safety for a biological body using tumor-bearing mice. This compound acted as a tubulin polymerization inhibitor stronger than nocodazole, and suppressed the growth of the tumor of the mice. Glycosides and polyethylene glycol esters of many kinds of both β-carboline and ellipticine derivatives were also synthesized to evaluate their hydrophilicity and lipophilicity in connection with antitumor activity.
Second, we advocated a new concept of the fluorous-solid phase (FSP) synthesis, using a macroreticular fluorous polystyrene resin, as a sustainable organic synthesis. This new methodology provides both high reactivity as an advantage of a liquid-phase reaction and easy separation of the product as that of a solid-phase reaction. Finally, we applied it to the synthesis of β-carboline derivatives.
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Report
(4 results)
Research Products
(117 results)
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[Journal Article] Synthesis and in vitro antitumor activity of novel 2-alkyl-5-methoxycarbonyl-11- methyl-6H-pyrido[4,3-b]carbazol-2-ium and 2-alkylellipticin-2-ium chloride derivatives2014
Author(s)
Ryota Mori, Asako Kato, Kousuke Komenoi, Haruaki Kurasaki, Touru Iijima, Masashi Kawagoshi, Y. B. Kiran, Shoichi Takeda, Norio Sakai, Takeo Konakahara
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Journal Title
Eur. J. Med. Chem.
Volume: 82
Pages: 16-35
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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