2014 Fiscal Year Final Research Report
Development of prodrugs based on a controlled reversible Michael reactions
| Project/Area Number |
25670051
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | プロドラッグ / 抗腫瘍活性 / 薬剤反応性 / マイケル付加 |
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| Outline of Final Research Achievements |
C5-curcuminoids are antitumor curcumin analogues bearing a reactive cross conjugated dienone structure. Dienone moiety is thought to be essential for antitumor activity and act as a Michael acceptor, which is traditionally avoided by medicinal chemists. Focusing on the dienone system, we monitored Michael reaction and retro Michael reaction between GO-Y030 and cysteamine by 1H-NMR spectroscopy method. In addition, we synthesized C5-curcuminoid thiol-adducts and evaluated their cell growth inhibitory activity against human colon cancer HCT116. The cytoxicity of C5-curcuminoid thiol-adduct was almost comparable with that of GO-Y030, highlighting their potential as prodrugs. Our results indicated that C5-curcuminoids react with cysteine thiol in a reversible manner, which is considered as important intracellular behavior of C5-curcuminoid.
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| Free Research Field |
創薬化学
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