首页> 外文期刊>Journal of enzyme inhibition and medicinal chemistry. >Synthesis, computational studies and assessment of in?vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII
【24h】

Synthesis, computational studies and assessment of in?vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII

机译:伞形基于肿瘤相关碳酸酐酶同种型IX和XII的umbelliferon基化合物的合成,计算研究和评估。

获取原文
           

摘要

Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11 , 15 , 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.
机译:香豆素是广泛扩散的二次代谢物,具有血红蛋白活性。已经确定香豆素代表了具有不同作用机制的人类碳酸酐酶(HCA)抑制剂的特殊类别,其涉及与铺设HCA催化位点入口的氨基酸残基的非典型结合。在此,我们报告了通过从间苯二酚衍生物和合适的β-酮酯开始通过经典Pechmann缩合制备的一小系列新的香豆素衍生物7-11,15,17的合成。抑制活性的评价表明,这些化合物具有纳米摩尔亲和力和对肿瘤相关的HCA IX和XII的高选择性在细胞溶质HCA I和HCA II同种型上。为了研究这些新的香豆素启动抑制剂的结合模式,将最活跃的化合物10和17对接在HCA XII催化裂缝中。

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