• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Aspartic vinyl sulfones: inhibitors of a caspase-3-dependent pathway.
【24h】

Aspartic vinyl sulfones: inhibitors of a caspase-3-dependent pathway.

机译：天冬氨酸乙烯砜：caspase-3依赖途径的抑制剂。

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

In this article we describe an expanded structure-activity relationship study for vinyl sulfones as caspase-3 inhibitors, a topic virtually unexplored in the existing literature. Most remarkably, and to our surprise, tripeptidyl vinyl sulfones were not active for caspase-3, opposite to other examples described in literature for peptidyl vinyl sulfones as potent cysteine protease inhibitors of clan CA. Moreover, the caspase-3 inhibitory activity of vinyl sulfones using an in vitro assay was then confirmed using a yeast cell-based assay. The results show that Fmoc-protected vinyl sulfones containing only the Asp moiety are inhibitors of a caspase-3-dependent pathway and the IC50 values obtained in the yeast assay are in the same order of magnitude of that obtained with the caspase-3 inhibitor tetrapeptidyl chloromethyl ketone, Ac-DEVD-CMK. This observation is consistent with appropriate cell permeability properties displayed by the vinyl sulfone inhibitors, as reflected by logP values ranging from 1.1 to 3.4. Overall, these results suggest that vinyl sulfones containing Asp at P1 should be considered for further optimization as caspase inhibitors and modulators of caspase-3-dependent pathways.
机译：在本文中，我们描述了作为caspase-3抑制剂的乙烯基砜的扩展的结构-活性关系研究，这是现有文献中几乎未曾探讨过的话题。最显着的是，令我们惊讶的是，三肽基乙烯基砜对caspase-3没有活性，这与文献中有关肽基乙烯基砜作为强效半胱氨酸蛋白酶抑制剂的文献中描述的其他实例相反。此外，然后使用基于酵母细胞的测定法，使用体外测定法证实了乙烯基砜的caspase-3抑制活性。结果表明，仅含有Asp部分的Fmoc保护的乙烯基砜是caspase-3依赖性途径的抑制剂，酵母分析中获得的IC50值与caspase-3抑制剂四肽基获得的IC50值处于相同的数量级。氯甲基酮，Ac-DEVD-CMK。该观察结果与乙烯基砜抑制剂所显示的适当的细胞通透性相一致，如logP值在1.1至3.4范围内。总体而言，这些结果表明，应进一步考虑在P1处含有Asp的乙烯基砜作为caspase抑制剂和caspase-3依赖性途径的调节剂。

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