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Research and development of bioactive natural products targeting cytoskeleton.

以细胞骨架为靶点的生物活性天然产物的研究与开发。

基本信息

批准号：
16310143
负责人：
KOBAYASHI Jun'ichi
金额：
$ 8.64万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310143/
关键词：
Actin Tubulin Molecular Target Natural Resource Read Compound

项目摘要

1)Eight stilbenoids, 1-(p-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (1), 2,7-dihydroxy-1,3-bis(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene (2), 4,7-dihydroxy-1-(p-hydroxyberzyl)-2-methoxy-9,10-dihydrophenanthrene (3), 3,3'-dihydroxy- 2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl (4), 3',5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (5), blestriarenes B (6) and C (7), and blestrianol A (8) have been isolated by the guidance of inhibitory effect of tubulin polymerization from the tubers of Bletilla striata (Orchidaceae). Among them, 4 and 5 inhibited the polymerization of tubulin at IC_<50> 10 μM, respectively. Furthermore 4 potentiated the cytotoxicity of SN-38 in BCRP-transduced K562 (K562/BCRP) cells.2)3D QSAR of rhazinilam (9), an alkaloid isolated from Rhazya stricta (Apocynaceae) with an activity involving disassembly of microtubules and its derivatives, was investigated by using the comparative molecular field analysis (CoMFA). In an effort to get a better under … More standing of the correlation between conformation and antitubulin activity of 9, most probable minimum energy conformation in solution of 9 was analyzed on the basis of NMR data of 9 in solution. The results indicated a correlation between the antitubulin activity of these alkaloids and the steric and electrostatic factors, which modulate their biological activity, and accounted for the potent activities of 9 with suitable relationship for the overall conformation.3)Solution conformations of amphidinolide H(10), a 26-membered macrolide exhibiting potent cytotoxic and antitumor activity, in CDCl_3 and DMSO-d_6 were investigated on the basis of NMR data, distance geometry calculation, and restrained energy minimization. Three-dimensional conformations in CDCl_3 were suggested to be close to the X-ray structure of 10, while those in DMSO-d_6 were indicated to be different from both those in CDCl_3 and the X-ray structure.4)Two new cytotoxic 26-membered macrolides, amphidinolides B4(11) and B5(12), have been isolated from a marine dinoflagellate Amphidinium sp.(strain Y-100), and the structures were elucidated on the basis of detailed analyses of 2D NMR data including 13C- 13C correlations. Less

1)8个二苯乙烯类化合物，1-(p-hydroxybenzyl)-4，8-dimethoxyphenanthrene-2，7-diol(1)，2，7-dihydroxy-1，3-bis(p-hydroxybenzyl)-4-methoxy-9，10-dihydrophenanthrene(2)，4，7-dihydroxy-1-(p-hydroxyberzyl)-2-methoxy-9，10-dihydrophenanthrene(3)，3，3‘-二羟基-2’，6‘-双(对羟基苯基)-5-甲氧基联苯(4)，3’，5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl(5)，Bestrienes B(6)和C(7)，在抑制微管蛋白聚合作用的指导下，从白头翁块茎中分离得到白藜芦醇A(8)。其中，4和5分别在IC50和10μM抑制微管蛋白的聚合。2)采用比较分子场分析(CoMFA)方法对罗布麻科植物罗布麻碱(9)的三维定量构效关系进行了研究。为了在…下取得更好的成绩根据9在溶液中的核磁共振数据，进一步分析了9的构象与抗微管蛋白活性的相关性，得到了9在溶液中最可能的最小能量构象。结果表明，这些生物碱的抗微管蛋白活性与调节其生物活性的立体和静电因素有关，并解释了9的有效活性。3)基于核磁共振数据、距离几何计算和限制能量最小化，研究了具有细胞毒性和抗肿瘤活性的26元大环内酯类化合物安息香内酯H(10)在CdCl3和DMSO-d6中的溶液构象。DMSO-d6的三维构象与CdCl3和DMSO-d6的结构不同。4)从海洋甲藻Amphiddium sp.(Y-100)中分离得到两个新的细胞毒性26元大环内酯化合物B4(11)和B5(12)，并对其结构进行了详细的二维核磁共振分析。较少