Wang Xuan, Jiang Xiaoye, Sun Shiyou, Liu Yongqiong
City College, Wuhan University of Science and Technology Wuhan 430000 China
RSC Adv. 2018 May 4;8(30):16494-16502. doi: 10.1039/c8ra02578a. eCollection 2018 May 3.
A strategy to develop chemotherapy agents by combining two complimentary chemo-active groups into a single molecule may have higher efficacy and fewer side effects than that of single-target drugs. In this article, we describe the synthesis and evaluation of a series of novel dual-acting levofloxacin-HDACi conjugates to target both histone deacetylase (HDAC) and tubulin polymerization. These bifunctional conjugates exhibited potent inhibitory activities against HDACs and tubulin polymerization. In docking analysis provides a structural basis for HDACs inhibition activities. Moreover, these conjugates showed selective anticancer activity that is more potent against MCF-7 compared to other four cancer cells A549, HepG2, PC-3, HeLa, but they had no toxicity toward normal cells.
将两个互补的化学活性基团结合到一个分子中以开发化疗药物的策略，可能比单靶点药物具有更高的疗效和更少的副作用。在本文中，我们描述了一系列新型双作用左氧氟沙星 - HDAC抑制剂共轭物的合成与评估，这些共轭物可同时作用于组蛋白脱乙酰酶（HDAC）和微管蛋白聚合。这些双功能共轭物对HDAC和微管蛋白聚合均表现出强效抑制活性。对接分析为HDAC抑制活性提供了结构基础。此外，这些共轭物显示出选择性抗癌活性，与其他四种癌细胞A549、HepG2、PC - 3、HeLa相比，对MCF - 7的抗癌活性更强，但对正常细胞无毒性。
