The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells
The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells
复制标题
Heck反应在选择性抑制耐药急性白血病细胞愈创木酚内酯倍半萜内酯衍生物合成中的应用
DOI：
10.1016/j.bmcl.2013.09.028
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发表时间：
2013-11-15
影响因子：
2.7
通讯作者：
Chen, Yue
中科院分区：
文献类型：
--
作者：
Ding, Ya-Hui;Fan, Hong-Xia;Chen, Yue
利用Heck反应合成了一系列α-亚甲基-γ-内酯部分芳基化的愈创木内酯型倍半萜内酯衍生物，并评价了它们对急性髓性白血病（AML）细胞株HL-60和阿霉素耐药细胞株HL-60/A的活性。尽管所有化合物对HL-60的活性均显著低于母体分子，但令人惊讶的是，化合物3a、4c-4 e、5e和8d显示出对阿霉素抗性细胞系HL-60/A的高效力（IC 50 = 6.2-19 μ M），并且它们对HL-60/A的活性与它们的母体分子相当。鉴于化合物5e具有抗HL-60/A的新活性，选择对HL-60/A具有抑制活性（IC 50 = 6.2 ± 0.5 μ M）的化合物5e进行初步机制研究。结果表明，化合物5e具有明显的诱导凋亡作用。(c)2013爱思唯尔有限公司保留所有权利。
A series of guaianolide-type sesquiterpene lactones derivatives with arylation of alpha-methylene-gamma-lactone moiety was synthesized using Heck reactions, and was evaluated for their activities against acute myelogenous leukemia (AML) cell line HL-60 and doxorubicin-resistant cell line HL-60/A. Although all compounds were significantly less active against HL-60 than the parent molecules, surprisingly, compounds 3a, 4c-4e, 5e, and 8d exhibited high potency against doxorubicin-resistant cell line HL-60/A (IC50 = 6.2-19 mu M), and their activities against HL-60/A were comparable to that of their parent molecules. In view of their novel activities against HL-60/A, compound 5e with inhibitory activity against HL-60/A (IC50 = 6.2 +/- 0.5 mu M) was selected for study its preliminary mechanism. The result reveals that compound 5e can obviously induce apoptosis. (c) 2013 Elsevier Ltd. All rights reserved.