...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Current Medicinal Chemistry >Thioredoxin System Modulation by Plant and Fungal Secondary Metabolites
【24h】

Thioredoxin System Modulation by Plant and Fungal Secondary Metabolites

机译：植物和真菌次生代谢物对硫氧还蛋白系统的调控

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

Thioredoxin (Trx) is the major cellular protein disulfide reductase in a broad range of organisms, including humans. Trx, together with glutaredoxin (Grx), plays critical roles in the regulation of cellular protein redox homeostasis. Reduced thioredoxin transfers reducing equivalents to disulphides in target proteins, leading to reversible oxidation of its active centre dithiol to a disulphide. The resulting disulphide bridge is, in turn, reduced to a dithiol by thioredoxin reductase (TrxR). Increasing attention has been paid to the role of Trx, as it has been shown to be a signalling intermediate beyond its intrinsic antioxidant activity. Indeed, this protein acts as a growth factor, activates a number of transcription factors regulating cell growth and survival, acts as cofactor for ribonucleotide reductase, and promotes angiogenesis. In addition, Trx has been demonstrated to cooperatively inhibit programmed cell death. Because of the multiple roles of Trx system in tumorigenesis, this protein represents an emerging target for anti-cancer drugs. Several Trx system modulators have been identified: a semi-synthetic Trx inhibitor, PX-12 (1-methylpropyl 2-imidazolyl disulfide), has been placed in a clinical trial. However, there is a growing interest in finding new selective ones. Natural products continue to provide structurally complex, but highly original lead structures for drug discovery programs: polyphenols, quinones, and terpenoids showed to affect the Trx/TrxR system at different levels. The purpose of this review is to provide an overview of the plant and fungal secondary metabolites interfering with Trx and TrxR activities, paying particularly attention to their mechanism of action. Among polyphenols, curcumin and some flavonoids such as myricetin and quercetin, have been identified as potential anticancer agents with a mechanism of action that may be mediated by the Trx system.
机译：硫氧还蛋白（Trx）是包括人类在内的各种生物中的主要细胞蛋白二硫键还原酶。 Trx与戊二醛（Grx）一起在细胞蛋白氧化还原稳态的调节中起关键作用。还原的硫氧还蛋白将还原的等价物转移到目标蛋白质中的二硫键上，从而导致其活性中心二硫醇可逆地氧化为二硫键。所得的二硫键又被硫氧还蛋白还原酶（TrxR）还原为二硫醇。 Trx的作用受到越来越多的关注，因为它已被证明是超越其固有的抗氧化剂活性的信号传导中间体。实际上，该蛋白充当生长因子，激活许多调节细胞生长和存活的转录因子，充当核糖核苷酸还原酶的辅因子，并促进血管生成。此外，Trx已被证明可以协同抑制程序性细胞死亡。由于Trx系统在肿瘤发生中的多种作用，该蛋白代表了抗癌药物的新兴靶标。已经确定了几种Trx系统调节剂：一种半合成Trx抑制剂PX-12（1-甲基丙基2-咪唑基二硫化物）已投入临床试验。但是，人们越来越有兴趣寻找新的有选择的人。天然产物继续为药物发现计划提供结构复杂但高度原始的先导结构：多酚，醌和类萜显示出在不同水平上影响Trx / TrxR系统的能力。这篇综述的目的是概述干扰Trx和TrxR活性的植物和真菌次生代谢产物，并特别注意它们的作用机理。在多酚中，姜黄素和一些类黄酮（如杨梅素和槲皮素）已被确定为潜在的抗癌药物，其作用机理可能由Trx系统介导。

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