| Co-Investigator(Kenkyū-buntansha) |
SATO Koichi Yarmaguchi University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90205914)
HORI Masatoshi The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (70211547)
MATSUNAGA Shigeki The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (60183951)
|
|---|
| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
|
|---|
| Research Abstract |
The aim of present study is that 1) examination of bioactivity of intermediary metabolite of cholesterol, such as farnesol, and marine sponge derived isoprenoid compounds, such as stellettamlde family, 2) analysis of relationship between chemical structure and bloactivilty in these compounds, and 3) clarification of new cell signaling pathway mediated by isoprenoid derivatives.
In the present study, we found that stellettamide A inhibits both calmodulin ability and L-type Ca channel activity. In contrast, farnesol inhibited only IL-type Ca channel activity.
We also isolated many asoprenoid compounds from marine toxin, such as stellettamide B, C, Stellettadine A, and Steliettazole A, B, C. The chemical structure-bioactivity relationship aanalysis in these stellettamide family lead. the hypotheyis to us that charge number in alkaloid part, length in isoprenoid chain and configuration between isoprenoid chain and alkaloid may be important for onset of calmodulin antagonistic action.
In another experiments, we also found several compounds to inhibit geranyltransferase, metaloprotease (MMP) in vitro. Massadine and Corticatic acids isolated from marine sponges specifically inhibited geranyitransferase type I. In contrast, Callysponginol sulfate A and Sodium 1-(12-hydroxy)octadecanyl sulfate inhibited MT-1 MMP and MMP2, respectively. These findings will hold the promise of new seed compounds for cancer, atherosclerosis and hypertension.
|
