| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We synthesized indole derivatives, and investigated the inhibition activity against protein tyrosine kinase (p60 c-Src). As a result, it was found that Compound 4 showed the strongest inhibition activity representing 1.34 μM IC_<50>. When we investigated the interaction between Compound 4 and the enzyme active site, it was shown that the strong interaction was exhibited between Compound 4 and the Lis 295 which is said to play an important role in the active site. We also synthesized 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives, and investigated the interaction between the synthesized derivatives and protein tyrosine kinase (p60 c-Src). It was found that inhibitory IC_<50> of Compound 12, 19. 13 represented 21.91, 21.20, 30.92 μM, respectively. These values are considered to be fairly well, although they are not in the best range. As for the docking simulation of those compounds, Compound 8, and 16 showed the strong affinity against the active site of the enzyme. Malaysian plant extract, Acalypha siamensis Olive. Ex Gage was obtained from collaborative researcher, and isolated each ingredient and the structure determination was performed by analytical instrument such as NMR, MS and so on. It was indicated that innovative compounds, Acalyphaser existed as chiral form of R, R, S or S, S, R. Docking simulation study between those compounds and protein tyrosine kinase (p60 c-Src) represented binding free energy of -5.97 kal/mol, and some showed the hydrogen bond against Hia58. It was extrapolated that IC_<50> values against human T-cell acute lymphoblastic leukemia (CCRF-HSB-2) and human oral epithermal carcinoma (KB) was 0.72 1.42 μM and 1.42 μM respectively.
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