Research and development of bioactive natural products targeting cytoskeleton.

1)八种二苯乙烯类化合物，1 -（对羟基苯基）-4,8-二甲氧基菲-2,7-二羟基-1,3-二（对羟基苯基）-4-甲氧基-9,10-二氢菲(2),4,7-二羟基-1-（对羟基苯基）-2-甲氧基-9,10-二氢菲(3),3,3'-二羟基-2 ',6'-二（对羟基苯基）-5-甲氧基联苯(4),3'，5-二羟基-2-（对羟基苯基）-3-甲氧基联苯(5),blestriarenes B(6)和C (7)，利用微管蛋白聚合抑制效应的指导，从白芨块茎中分离得到了blestrianol A(8)。其中，4和5分别在IC_<50 bb_0 10 μM处抑制微管蛋白的聚合。此外，4增强了SN-38在BCRP转导的K562 （K562/BCRP）细胞中的细胞毒性。2)采用比较分子场分析（CoMFA）方法研究了罗布麻属植物中具有微管分解活性的生物碱rhazinilam(9)的三维QSAR。为了更好地了解9的构象与抗微管蛋白活性之间的关系，根据9在溶液中的核磁共振数据，分析了9在溶液中最可能的最小能构象。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位阻因子和静电因子之间存在一定的相关性，并与总体构象之间存在一定的关系。3)基于核磁共振数据、距离几何计算和约束能量最小化，研究了具有强细胞毒和抗肿瘤活性的26元大环内酯类化合物amphidinolide H（10）在CDCl_3和DMSO-d_6中的溶液构象。CDCl_3中的三维构象接近于10的x射线结构，而DMSO-d_6中的三维构象与CDCl_3中的三维构象和x射线结构都不同。4)从海洋双鞭毛藻Amphidinium sp.（菌株Y-100）中分离到两个新的细胞毒性26元大环内酯类化合物amphidinolides B4（11）和B5(12)，并通过详细的二维NMR数据（13C- 13C相关性）对其结构进行了鉴定。少

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