• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Drug Design, Development and Therapy >Synthesis and Biological Evaluations of Monocarbonyl Curcumin Inspired Pyrazole Analogues as Potential Anti-Colon Cancer Agent
【24h】

Synthesis and Biological Evaluations of Monocarbonyl Curcumin Inspired Pyrazole Analogues as Potential Anti-Colon Cancer Agent

机译：单羰基姜黄素激发吡唑类似物作为潜在抗结肠癌剂的合成和生物学评价

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Purpose: The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities. Methods: Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound 7h exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis. Results: The ICsub50/sub value of 7h against SW620 cells was 12 nM, being more potent than curcumin (ICsub50/sub = 9.36 μM), adriamysin (ICsub50/sub = 3.28 μM) and oxaliplatin (ICsub50/sub = 13.33 μM). Further assays showed that 7h inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that 7h decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells. Conclusion: A new MCACs 7h was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that 7h exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that 7h was a promising candidate as an anti-colon cancer drug for future development.
机译：目的：姜黄素（MCACS）的甘油基类似物已被广泛研究其有前途的抗肿瘤活性。吡唑是一种五元芳族杂环体系，具有常用于药物中的各种生物活性。然而，研究了很少的MCACS启发吡唑类似物。为了基于MCACS寻找更多有效的细胞毒性剂，合成了一系列新的1,5-二芳基/杂芳基-1,4-五胺-3-吡唑部分的吡唑部分，并评估其抗结肠癌活动。方法：通过光谱基准合成十五个新化合物，并通过光谱基准进行，然后通过MTT测定预先通过MTT测定对其对四种人类癌细胞系的面板进行细胞毒性活性进行测试，即胃（SGC-7901），肝脏（Hepg2），肺（A549）和结肠（SW620）癌细胞。化合物7h在这15种化合物中表现出优异的选择性和优异的SW620细胞的抗增殖活性。此外，通过Transwell迁移和侵袭测定，克隆基测定，细胞凋亡分析，细胞循环分析，Western印迹分析来研究所述机制。结果：对SW620细胞7H的IC 50 值为12nm，比姜黄素更有效（IC 50 =9.36μm），Adriamysin（IC 50 < /亚> =3.28μm）和oxaliplatin（IC 50 =13.33μm）。进一步的测定表明，7H抑制SW620细胞迁移，侵袭和菌落形成明显是由于其在G2 / m和S阶段和凋亡中诱导细胞周期停滞的能力。 Western印迹测定显示，7h降低了ATM基因的蛋白质表达，这可能主要有助于其对SW620细胞的抗癌活性。结论：合成了新的MCACS 7H，发现对SW620细胞具有优异的抗增殖活性。进一步的研究表明，7h对SW620细胞的抗癌活性可能通过降低atm蛋白表达来施加抗SW620细胞。本研究表明，7h是一个有前途的候选者，作为抗结肠癌药物，用于未来发展。

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