Vitamin E analogues as inducers of apoptosis: structure-function relation.
Vitamin E analogues as inducers of apoptosis: structure-function relation.
复制标题
DOI：
10.1038/sj.bjc.6600981
复制
发表时间：
2003-06-16
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
最近的研究表明α-生育酚琥珀酸酯（α-TOS）是一种具有抗凋亡活性的促凋亡剂。由于维生素E（VE）分子的修饰可能会影响其致肿瘤活性，我们使用恶性细胞系测试了一些新合成的VE类似物。芳环上甲基取代数较少的α-TOS类似物的活性低于α-TOS。用马来酰基取代琥珀酰基大大提高了活性，而戊二酰基酯的活性较低。α-TOS和δ-TOS上游离琥珀酰羧基的甲基化完全阻止了母体化合物的致突变活性。Trolox及其琥珀酰化衍生物均无活性。α-生育三烯酚（α-T3 H）不能诱导细胞凋亡，而γ-T3 H则具有促凋亡作用，琥珀酰化后更是如此。将γ-T3的脂肪族侧链缩短一个异戊二烯基单元可提高其活性。无论是植基或油基琥珀酸引起细胞凋亡。这些发现表明，VE分子的不同功能部分的修饰可以增强致突变活性。希望这些观察结果将导致合成具有更高的致炎性的类似物，从而具有更高的抗肿瘤功效。
Recent results show that α-tocopheryl succinate (α-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of α-TOS with lower number of methyl substitutions on the aromatic ring were less active than α-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on α-TOS and δ-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. α-tocotrienol (α-T3 H) failed to induce apoptosis, while γ-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of γ-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.
登录
查看更多内容
影响因子：
3.5
作者：
Neuzil, J;Svensson, I;Brunk, UT
通讯作者：
Brunk, UT
影响因子：
8.8
作者：
Neuzil J;Weber T;Gellert N;Weber C
通讯作者：
Weber C
影响因子：
4.8
作者：
Neuzil, J;Weber, T;Weber, C
通讯作者：
Weber, C
影响因子：
2.9
作者：
Weber, T;Dalen, H;Neuzil, J
通讯作者：
Neuzil, J
DOI：
10.1152/ajpgi.2001.280.1.g95
发表时间：
2001-01-01
影响因子：
4.5
作者：
Borel, P;Pasquier, B;Azais-Braesco, V
通讯作者：
Azais-Braesco, V