2013 Fiscal Year Final Research Report
Synthetic study of novel antitumor agents
| Project/Area Number |
22390021
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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 |
Drug development chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Tetsuaki 大阪大学, 薬学研究科(研究院), 名誉教授 (40116059)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Naoto 京都薬科大学, 薬学部, 講師 (90420413)
MIYOSHI Hideto 京都大学, 大学院農学研究科, 教授 (20190829)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMORI Takao がん研究会, がん化学療法センター 分子薬理部, 客員研究員 (60200854)
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| Project Period (FY) |
2010-04-01 – 2013-03-31
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| Keywords | 抗がん剤 / 有機合成化学 / 生物活性物質 / 構造活性相関 |
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| Research Abstract |
Annonaceous acetogenins are polyketides featuring one to three tetrahydrofuran ring(s) connected an alpha,beta-unsaturated-gamma-lactone ring via a long hydrocarbon chain. They exhibit an antitumor activity, owing to the inhibition of mitochondrial NADH ubiquinone oxidoreductase (complex I). We were interested in structural and biological similarities between acetogeinns and pesticides targeting complex I, and designed hybrid molecules of them. Now, we revealed that the thiophen analogue showed potent inhibitory activities against human cancer cell lines.
The convergent synthesis of three C35-fluorinated analogues of solamin, a mono-THF acetogenin, has also been achieved. As a result, it was revealed that the number of fluorine atoms on the gamma-lactone moiety affects the growth inhibitory activity against human cancer cell lines, indicating that the gamma-lactone moiety in acetogenins may play an important role in the interaction between acetogenins and the target molecules.
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