Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU
Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU
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基于 HDAC 抑制剂 MS-275 和 5-FU 的多靶点抗癌药物的发现
DOI：
10.2174/1573406411666150714111045
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发表时间：
2016-01-01
影响因子：
2.3
通讯作者：
Zhang, Yingjie
中科院分区：
文献类型：
--
作者：
Jiang, Yuqi;Li, Xiaoguang;Zhang, Yingjie
组蛋白脱乙酰酶 (HDAC) 抑制剂具有针对癌细胞的多种作用，已成为具有广泛应用前景的癌症治疗药物之一。 HDAC 抑制剂与细胞毒性氟尿嘧啶 (5-FU) 的组合在体外和体内均显示出相加和协同效应。为了探索在单一分子结构中结合两个生物活性基团的二价药物在癌症治疗中的可能性，我们通过将临床 HDAC 抑制剂 MS-275 的生物活性片段与细胞毒剂 5-FU 结合，设计并合成了新的双重作用化合物。目标化合物 9a 和 9b 显示出与 MS-275 相当的 HDAC 抑制作用，并对六种癌细胞系具有中等抗增殖活性。
Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.