Department of Inorganic and Analytical Chemistry, Medical University of Bialystok, Bialystok, Poland.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):362-371. doi: 10.1080/14756366.2020.1867121.
One of the systems responsible for maintaining cellular redox homeostasis is the thioredoxin-dependent system. An equally important function of this system is the regulation of the expression of many proteins by the transcription factor NF-κB or the apoptosis regulating kinase (ASK-1). Since it has been shown that the Trx-dependent system can contribute to both the enhancement of tumour angiogenesis and growth as well as apoptosis of neoplastic cells, the search for compounds that inhibit the level/activity of Trx and/or TrxR and thus modulate the course of the neoplastic process is ongoing. It has been shown that many naturally occurring polyphenolic compounds inactivate elements of the thioredoxin system. In addition, the effectiveness of Trx is inhibited by imidazole derivatives, while the activity of TrxR is reduced by transition metal ions complexes, dinitrohalobenzene derivatives, Michael acceptors, nitrosourea and ebselen. In addition, research is ongoing to identify new selective Trx/TrxR inhibitors.
一个负责维持细胞氧化还原稳态的系统是依赖硫氧还蛋白的系统。该系统的一个同样重要的功能是通过转录因子 NF-κB 或凋亡调节激酶 (ASK-1) 调节许多蛋白质的表达。由于已经表明，依赖硫氧还蛋白的系统可以促进肿瘤血管生成和生长以及肿瘤细胞的凋亡，因此正在寻找可以抑制 Trx 和/或 TrxR 的水平/活性的化合物，从而调节肿瘤过程的进程。已经表明，许多天然存在的多酚化合物使硫氧还蛋白系统的元素失活。此外，咪唑衍生物抑制 Trx 的有效性，而过渡金属离子配合物、二硝基卤代苯衍生物、迈克尔受体、亚硝脲和 ebselen 降低 TrxR 的活性。此外，正在进行研究以确定新的选择性 Trx/TrxR 抑制剂。
