...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>European journal of pharmaceutical sciences >Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity
【24h】

Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity

机译：芳基甲基甲醛哌啶和哌嗪基羟肟酸盐作为潜在HDAC8抑制剂的设计，合成，生物学评价及分子对接研究抗癌活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

HDAC8 has been established as one of the vital targets as far as the cancer is concerned. Different compounds having potential HDAC inhibitory activity have been approved by USFDA. However, none of these compounds are selective towards specific HDAC isoform. In this current study, some new hydroxamate derivatives with alkylpiperidine and alkylpiperazine linker moieties have been designed, synthesized and biologically evaluated. All these compounds are effective HDAC8 inhibitors comprising more or less similar cytotoxic potential against different cancer cell lines. It is observed that the piperazine scaffold containing compound is more active than the compound with piperidine scaffold for exerting HDAC8 inhibitory activity. Moreover, the 4-quinolyl cap group is better than the biphenyl group which is better than the benzyl group for producing higher HDAC8 inhibition as well as cytotoxicity. These compounds displayed selective HDAC8 inhibition over HDAC3. Moreover, these compounds showed an increased caspase3/7 activity suggesting their anticancer potential through modulation of apoptotic pathways. Molecular docking study with three potent compounds was performed with both HDAC3 and HDAC8 enzymes to understand the selectivity profile of these compounds. Compound containing 4-quinolyl cap group with alkyl piperazinyl urea linker moiety has been emerged out as the lead molecule that may be further modified to design more effective and selective HDAC8 inhibitors in future.
机译：就癌症而言，HDAC8已被建立为重要目标之一。 USFDA批准了具有潜在HDAC抑制活性的不同化合物。然而，这些化合物中没有任何均针对特定的HDAC同种型选择性。在本前研究中，设计了一些新的羟肟酸盐衍生物，具有烷基哌啶和烷基哌嗪连接部分，合成和生物学评价。所有这些化合物都是有效的HDAC8抑制剂，其包含对不同癌细胞系的或多或少类似的细胞毒性潜力。观察到含有哌嗪支架的化合物比具有哌啶支架的化合物更有效，用于施加HDAC8抑制活性。此外，4-喹啉基盖组优于苯甲基，优于苄基，用于生产较高的HDAC8抑制以及细胞毒性。这些化合物在HDAC3上显示出选择性HDAC8抑制。此外，这些化合物显示了通过调节凋亡途径来提高Caspase3 / 7活性，这表明它们的抗癌潜力。用HDAC3和HDAC8酶进行三种有效化合物的分子对接研究，以了解这些化合物的选择性曲线。含有烷基哌嗪基脲链接剂部分的含有4-喹啉帽基的化合物作为铅分子，可以进一步修饰以在将来设计更有效和选择性HDAC8抑制剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号