当前位置: X-MOL 学术Chem. Res. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Inhibition of Thioredoxin Reductase by Triosmium Carbonyl Clusters.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-07-28 , DOI: 10.1021/acs.chemrestox.0c00214
Wei Xiang Koh 1 , Lucia Coppo 2 , Arne Holmgren 2 , Jia Wen Kong 1 , Weng Kee Leong 1
Affiliation  

Tumor cells are characterized by increased reactive oxygen species production in parallel with an enhanced antioxidant system to avoid oxidative damage. The inhibition of antioxidant systems is an effective way to kill cancer cells, and the thioredoxin system or, more specifically, the cytosolic selenocysteine-containing enzyme thioredoxin reductase (TrxR) has become an interesting target for cancer therapy. We show here that the known cytotoxic and apoptosis-inducing osmium carbonyl cluster Os3(CO)10(NCCH3)2 (1) is a nonsubstrate inhibitor of mammalian TrxR, with an IC50 of 5.3 ± 0.9 μM. It inhibits TrxR selectively over the closely related glutathione reductase (GR) and in the presence of excess reduced glutathione (GSH). This inhibition has also been demonstrated in cell lysates, suggesting that TrxR inhibition is a potential apoptotic pathway for 1.

中文翻译:

羰基三锇簇对硫氧还蛋白还原酶的抑制。

肿瘤细胞的特征是活性氧产生增加,同时抗氧化系统增强以避免氧化损伤。抑制抗氧化系统是杀死癌细胞的有效方法,硫氧还蛋白系统,或者更具体地说,含有细胞溶质硒代半胱氨酸的酶硫氧还蛋白还原酶 (TrxR) 已成为癌症治疗的一个有趣目标。我们在这里展示了已知的细胞毒性和诱导细胞凋亡的锇羰基簇 Os 3 (CO) 10 (NCCH 3 ) 2 ( 1 ) 是哺乳动物 TrxR 的非底物抑制剂,IC 505.3 ± 0.9 μM。它通过密切相关的谷胱甘肽还原酶 (GR) 和在存在过量还原型谷胱甘肽 (GSH) 的情况下选择性地抑制 TrxR。这种抑制作用也已经证明在细胞裂解物,表明的TrxR抑制为潜在的细胞凋亡途径1
更新日期:2020-09-21
down
wechat
bug