...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Chemical synthesis, pharmacological evaluation and in silico analysis of new 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives as potential anti-mitotic agents
【24h】

Chemical synthesis, pharmacological evaluation and in silico analysis of new 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives as potential anti-mitotic agents

机译：新的2,3,3a，4,5,6-六氢环戊[c]吡唑衍生物作为潜在的抗有丝分裂剂的化学合成，药理学评估和计算机分析

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

We have synthesized new, biologically active mono-and di-substituted 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives bearing electron withdrawing groups and electron donating groups. These derivative structures were characterized by their spectral and analytical data. The newly synthesized hexahydropyrazole analogues were evaluated for their in vitro anticancer activity against breast and lung cancer cell lines using a cytotoxicity bioassay. To understand their mechanism of action, tubulin binding assays were performed which pointed to their binding to microtubules in a mode similar to but not identical to colchicine, as evidenced by their K-D value evaluation. Computational docking studies also suggested binding near the colchicine binding site on tubulin. These results were further confirmed by colchicine-binding assays on the most active compounds, which indicated that they bound to tubulin near but not at the colchicine site. The moderate cytotoxic effects of these compounds may be due to the presence of electron donating groups on the para-position of the phenyl ring, along with the hexahydropyrazole core nucleus. The observed anti-cancer activity based on inhibition of microtubule formation may be helpful in designing more potent compounds with a hexahydropyrazole moiety. (C) 2016 Elsevier Ltd. All rights reserved.
机译：我们已经合成了带有吸电子基团和给电子基团的新的，具有生物活性的单和双取代的2,3,3a，4,5,6-六氢环戊[c]吡唑衍生物。这些衍生结构的特征在于其光谱和分析数据。使用细胞毒性生物测定法评估了新合成的六氢吡唑类似物对乳腺癌和肺癌细胞系的体外抗癌活性。为了了解它们的作用机理，进行了微管蛋白结合测定，指出它们以与秋水仙碱相似但不相同的方式与微管结合，如通过其K-D值评估所证明的。计算对接研究还表明在微管蛋白上秋水仙碱结合位点附近有结合。这些结果通过最活性化合物的秋水仙碱结合试验进一步证实，这表明它们与秋水仙碱位点附近但未结合的微管蛋白结合。这些化合物的中等细胞毒性作用可能是由于在苯环对位的电子给体以及六氢吡唑核心核的存在。基于抑制微管形成而观察到的抗癌活性可能有助于设计具有六氢吡唑部分的更有效的化合物。 （C）2016 Elsevier Ltd.保留所有权利。

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