TRFS-green | 1513848-14-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: TRFS-green
• 英文别名: dithiolan-4-yl N-(2-butyl-1,3-dioxobenzo[de]isoquinolin-6-yl)carbamate
• CAS: 1513848-14-0
• 化学式: C₂₀H₂₀N₂O₄S₂
• 分子量: 416.522
• InChiKey: MUAYCZWBPDUZKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  苊 在 盐酸 、 sodium dichromate 、 tin(II) chloride dihdyrate 、 硝酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 30.0h， 生成 TRFS-green
  参考文献：
  名称：

  Highly Selective Off–On Fluorescent Probe for Imaging Thioredoxin Reductase in Living Cells

  摘要：

  The first fluorescent probe for mammalian thioredoxin reductase (TrxR), TRFS-green, was designed, synthesized, and fully evaluated. The probe features a 1,2-dithiolane scaffold with a quenched naphthalimide fluorophore. TRFS-green displays a green fluorescence off on change induced by the TrxR-mediated disulfide cleavage and subsequent intramolecular cyclization to liberate the masked naphthalimide fluorophore. It was demonstrated in vitro that TRFS-green manifests high selectivity toward TrxR over other related enzymes and various small molecule thiols as well as biological reducing molecules. HPLC analyses indicated that TRFS-green was exclusively converted to naphthalimide catalyzed by TrxR. The ability in triggering on the fluorescence signal by cellular protein extracts correlates well with the endogenous TrxR activity in different cells. Furthermore, inhibition of TrxR by 2,4-dinitrochlorobenzene or depletion of TrxR by immunoprecipitation remarkably decreases the reduction of TRFS-green by cellular protein extracts. Finally, TRFS-green was successfully applied in imaging TrxR activity in living cells. The fluorescence signal of TRFS-green in living cells was inhibited by pretreating the cells with TrxR inhibitor in a dose-dependent manner, potentiating the development of living cell-based screening assay for identifying TrxR inhibitors. We expect the novel fluorescent probe TRFS-green would facilitate the discovery of TrxR-targeting small molecules for potential therapeutic agents and provide significant advances in understanding the physiological/pathophysiological functions of TrxR in vivo.

  DOI：

  10.1021/ja408792k

文献信息

• Design, synthesis, and biological evaluation of a novel indoleamine 2,3-dioxigenase 1 (IDO1) and thioredoxin reductase (TrxR) dual inhibitor
  作者：Qing-Zhu Fan、Ji Zhou、Yi-Bao Zhu、Lian-Jun He、Dong-Dong Miao、Sheng-Peng Zhang、Xiao-Ping Liu、Chao Zhang

  DOI：10.1016/j.bioorg.2020.104401

  日期：2020.12

  cancer immunotherapy. Thioredoxin reductase (TrxR) enzymes are reactive oxygen species (ROS) modulators that are involved in the tumor cell growth and survival processes. The 4-phenylimidazole scaffold is well-established as useful for indoleamine 2,3-dioxygenase 1 (IDO1) inhibition, while piperlongumine (PL) and its derivatives have been reported to be inhibitors of TrxR. To take advantage of both

  靶向 Trp-Kyn 通路是一种有吸引力的癌症免疫治疗方法。硫氧还蛋白还原酶 (TrxR) 酶是活性氧 (ROS) 调节剂，参与肿瘤细胞生长和存活过程。4-苯基咪唑支架已被证实可用于抑制吲哚胺 2,3-双加氧酶 1 (IDO1)，而胡椒碱 (PL) 及其衍生物据报道是 TrxR 的抑制剂。为了同时利用免疫疗法和 TrxR 抑制，我们使用 4-苯基咪唑和 PL 支架的结构组合设计了第一代 IDO1 和TrxR双重抑制剂 ( ZC0101 )。ZC0101在体外对 IDO1 和TrxR表现出更好的双重抑制作用并且在细胞酶测定中比未结合形式的 4-苯基咪唑和 PL。它还在各种癌细胞系中显示出抗增殖活性，并在正常细胞和癌细胞之间具有选择性杀伤作用。此外，ZC0101有效诱导癌细胞凋亡和 ROS 积累。在ZC0101处理期间，TrxR1 和 IDO1 表达的敲低诱导细胞酶抑制和 ROS 积累效应，但只有降低
• Highly Selective Off–On Fluorescent Probe for Imaging Thioredoxin Reductase in Living Cells
  作者：Liangwei Zhang、Dongzhu Duan、Yaping Liu、Chunpo Ge、Xuemei Cui、Jinyu Sun、Jianguo Fang

  DOI：10.1021/ja408792k

  日期：2014.1.8

  The first fluorescent probe for mammalian thioredoxin reductase (TrxR), TRFS-green, was designed, synthesized, and fully evaluated. The probe features a 1,2-dithiolane scaffold with a quenched naphthalimide fluorophore. TRFS-green displays a green fluorescence off on change induced by the TrxR-mediated disulfide cleavage and subsequent intramolecular cyclization to liberate the masked naphthalimide fluorophore. It was demonstrated in vitro that TRFS-green manifests high selectivity toward TrxR over other related enzymes and various small molecule thiols as well as biological reducing molecules. HPLC analyses indicated that TRFS-green was exclusively converted to naphthalimide catalyzed by TrxR. The ability in triggering on the fluorescence signal by cellular protein extracts correlates well with the endogenous TrxR activity in different cells. Furthermore, inhibition of TrxR by 2,4-dinitrochlorobenzene or depletion of TrxR by immunoprecipitation remarkably decreases the reduction of TRFS-green by cellular protein extracts. Finally, TRFS-green was successfully applied in imaging TrxR activity in living cells. The fluorescence signal of TRFS-green in living cells was inhibited by pretreating the cells with TrxR inhibitor in a dose-dependent manner, potentiating the development of living cell-based screening assay for identifying TrxR inhibitors. We expect the novel fluorescent probe TRFS-green would facilitate the discovery of TrxR-targeting small molecules for potential therapeutic agents and provide significant advances in understanding the physiological/pathophysiological functions of TrxR in vivo.