Research and development of bioactive natural products targeting cytoskeleton.

1)8个芪类化合物，1-（p-hydroxybenzyl）-4，8-dimethoxyphenanthrene-2，7-diol（1），2，7-dihydroxy-1，3-bis（对羟基苄基）-4-甲氧基-9，10-二氢菲（2），4，7-二羟基-1-（p-hydroxyberzyl）-2-methoxy-9，10-dihydrophenanthrene（3），3，3'-dihydroxy-2'，6'-bis（对羟基苄基）-5-甲氧基联苄基（4），3 '，5-二羟基-2-（对羟基苄基）-3-甲氧基联苄基（5），泡甾芳烃B（6）和C（7），从白及（Bletilla striata）块茎中分离得到3个具有微管蛋白聚合抑制作用的化合物，其中3个为Blestrianol A（8），另1个为Blestrianol A（8）。其中化合物4和化合物5抑制微管蛋白聚合的IC_（<50>10）μM。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）通过使用比较分子场分析（CoMFA）研究了从Rhazya stricta（夹竹桃科）中分离的生物碱rhazinilam（9）的3D QSAR。为了更好地了解 关于我们 从构象与抗微管蛋白活性的相关性出发，根据9在溶液中的NMR数据，分析了9在溶液中的最可能最小能量构象。结果表明这些生物碱的抗微管蛋白活性与空间和静电因素之间存在相关性，空间和静电因素调节它们的生物活性，并解释了9的有效活性与整体构象的适当关系。3）具有有效细胞毒性和抗肿瘤活性的26元大环内酯amphidinophenol H（10）的溶液构象，在CDCl_3和DMSO-d_6中的NMR数据、距离几何计算和约束能量最小化的基础上，研究了它们在CDCl_3和DMSO-d_6中的反应。从海洋甲藻Amphidinium sp.中分离得到两个新的具有细胞毒性的26元大环内酯类化合物：Ampidinolides B4（11）和B5（12）。（菌株Y-100），并根据2D NMR数据（包括13 C-13 C相关性）的详细分析，阐明了其结构。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