• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Synthesis of tricyclic carbohydrate-benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains
【24h】

Synthesis of tricyclic carbohydrate-benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains

机译：三环碳水化合物 - 苯杂交种作为半抗凝蛋白-1和半抗凝蛋白-8 n末端结构域的选择性抑制剂

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

As the galactoside binding family of galectin proteins is involved in many physiological and pathological processes, the inhibitors of these proteins are considered to be of significant interest in the treatment of diseases such as cancer and fibrosis. Herein, fused tricyclic carbohydrate-benzene hybrid core structures are reported to be the selective inhibitors of galectin-1 and the N-terminal domain of galectin-8 by a competitive fluorescence polarization assay. The key intermediates mono- or diiodo tricyclic carbohydrate-benzene hybrids were synthesized from protected 2-bromo-3-O-propargyl-d-galactose via a domino reaction and subsequently utilized for further derivatization by Stille couplings to achieve derivatives carrying substituents at C10 and/or C11. Several compounds showed affinity for the galectin-1 and galectin-8 N-terminal (8N) domains; however, weak or even no binding was observed for galectin-3. Monosubstituted derivatives at C10 or C11 exhibited better affinity for galectin-8N than di-substituted derivatives at C10 or C11. Especially, a benzyl substituent or p-fluorobenzyl substituent at C11 displayed affinity and selectivity for galectin-1 and galectin-8N over galectin-3. This suggests that tricyclic carbohydrate-benzene hybrids are promising scaffolds for the development of selective galectin-1 and galectin-8N inhibitors.
机译：随着半乳糖蛋白蛋白的半乳糖苷结合家族涉及许多生理和病理过程，这些蛋白质的抑制剂被认为对治疗癌症和纤维化等疾病的患者具有重要兴趣。这里，据报道，融合的三环碳水化合物 - 苯杂化核心结构是通过竞争性荧光偏振测定的半抗凝蛋白-1和半抗凝蛋白-8的N-末端结构域的选择性抑制剂。关键中间体单碘或二碘三环碳水化合物 - 苯杂交物通过多米诺反应从受保护的2-溴-3-O-丙基-GARGYL-D-半乳糖合成，随后通过STILLE联轴器进一步用于进一步衍生化，以在C10和C10中实现携带取代基的衍生物/或c11。几种化合物对Galectin-1和Galectin-8 N-末端（8N）结构域具有亲和力;然而，对于Galectin-3，观察到弱甚至没有结合。 C10或C11的单取出的衍生物对G10或C11的二取代衍生物具有更好的亲眼性亲和力。特别是，在C11的苄基取代基或对氟苄基取代基显示在Galectin-3上的G11和Galectin-8N的亲和力和选择性。这表明三环碳水化合物 - 苯杂交物是有前途的支架，用于开发选择性Galectin-1和Galectin-8N抑制剂。

著录项

  • 来源
    《RSC Advances》 |2020年第33期|共7页
  • 作者

    Wu Chunxia; Yong Can; Zhong Qiuju; Wang Zhouyu; Nilsson Ulf J.; Zhang Yuanyuan;

  • 作者单位

    Xihua Univ Sch Sci Chengdu 610039 Peoples R China;

    Xihua Univ Sch Sci Chengdu 610039 Peoples R China;

    Xihua Univ Sch Sci Chengdu 610039 Peoples R China;

    Xihua Univ Sch Sci Chengdu 610039 Peoples R China;

    Lund Univ Dept Chem Ctr Anal &

    Synth POB 124 SE-22100 Lund Sweden;

    Xihua Univ Sch Sci Chengdu 610039 Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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