2014 Fiscal Year Final Research Report
Development of prodrugs based on a controlled reversible Michael reactions
Project/Area Number |
25670051
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Drug development chemistry
|
Research Institution | Tohoku University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Keywords | プロドラッグ / 抗腫瘍活性 / 薬剤反応性 / マイケル付加 |
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.
|
Free Research Field |
創薬化学
|