Small structural changes of pentacyclic lupane type triterpenoid derivatives lead to significant differences in their anticancer properties
Small structural changes of pentacyclic lupane type triterpenoid derivatives lead to significant differences in their anticancer properties
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DOI：
10.1016/j.ejmech.2010.04.018
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发表时间：
2010-08-01
影响因子：
6.7
通讯作者：
Paschke, Reinhard
中科院分区：
文献类型：
--
作者：
Kommera, Harish;Kaluderovic, Goran N.;Paschke, Reinhard
本文合成了五种新的桦木酸和桦木酮酸衍生物，并研究和讨论了结构变化对抗癌活性的影响。桦木酸和桦木酮酸衍生物的抗增殖活性进行了研究，对不同组织起源的八种肿瘤细胞系。该衍生物在微摩尔浓度下对靶肿瘤细胞系产生剂量依赖性抗增殖作用。活性最强的化合物5，2-氨基-3-羟基-2-（羟甲基）丙基（3-O-乙酰基）桦木酸酯和9，2-氨基-3-羟基-2-（羟甲基）丙基桦木酸酯诱导结肠癌细胞系HT-29的细胞死亡的凋亡模式。用5和9处理HT-29细胞诱导凋亡，如通过染料排除试验（台盼蓝）和通过在DNA片段化测定和FITC膜联蛋白V测定中出现典型的梯状图案所观察到的。还呈现了由化合物5引起的细胞周期扰动。(C)2010年Elsevier Masson SAS。All rights reserved.
In the present investigations five new derivatives of betulinic and betulonic acid were synthesized and the effect of this structural variations on anticancer activity was studied and discussed. The antiproliferative activity of betulinic and betulonic acid derivatives was studied against eight tumor cell lines of different histogenic origin. The derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. The apoptotic mode of cell death on colon cancer cell line HT-29 was induced by the most active compounds 5, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl (3-O-acetyl)betulinate, and 9, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl betulonate. Treatment of HT-29 cells with 5 and 9 induced apoptosis, as observed by dye exclusion test (trypan blue) and by the appearance of a typical ladder pattern in the DNA fragmentation assay and FITC annexin V assay. Cell cycle perturbations caused by compound 5 are also presented. (C) 2010 Elsevier Masson SAS. All rights reserved.