Characterisation of naturally occurring isothiocyanates as glutathione reductase inhibitors.
Characterisation of naturally occurring isothiocyanates as glutathione reductase inhibitors.
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天然存在的异硫氰酸酯作为谷胱甘肽还原酶抑制剂的表征
DOI：
10.1080/14756366.2020.1822828
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发表时间：
2020-12
影响因子：
5.6
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Li X;Ni M;Xu X;Chen W
摘要谷胱甘肽还原酶（GR）是抗氧化应激的重要抗氧化酶，已成为抗肿瘤和抗疟疾药物开发的重要靶点。在这方面，我们评估了天然存在的异硫氰酸酯作为有前途的GR抑制剂，并阐明了作用机制。异硫氰酸苄酯（BITC）和异硫氰酸苯乙酯（PEITC）对酵母GR（yGR）和人GR（hGR）的抑制作用具有时间和浓度依赖性。BITC对yGR的Ki和kinact分别为259.87 µM和0.0266 min−1。GR抑制仅在NADPH存在下发生，并在广泛透析后持续存在。串联质谱分析表明，Cys61，而不是Cys66的活性位点的yGR是单苄基硫代氨基甲酰化的BITC。还观察到BITC和PEITC在培养的癌细胞中对细胞内GR的抑制。BITC和PEITC被评价为GR的竞争性和不可逆抑制剂。
Abstract Glutathione reductase (GR), an essential antioxidant enzyme against oxidative stress, has become an attractive drug target for the development of anticancer and antimalarial drugs. In this regard, we evaluated the naturally occurring isothiocyanates as promising GR inhibitors and elucidated the mechanism of action. It was found that benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) inhibited yeast GR (yGR) and human GR (hGR) in a time- and concentration-dependent manner. The Ki and kinact of BITC against yGR were determined to be 259.87 µM and 0.0266 min−1, respectively. The GR inhibition occurred only in the presence of NADPH and persisted after extensive dialysis. The tandem mass spectrometric analysis revealed that Cys61 rather than Cys66 at the active site of yGR was mono-benzyl thiocarbamoylated by BITC. Inhibition of intracellular GR by BITC and PEITC in cultured cancer cells was also observed. BITC and PEITC were evaluated as competitive and irreversible inhibitors of GR.
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异硫氰酸丙酯通过谷胱甘肽消耗导致氧化应激诱导胃癌细胞凋亡
影响因子：
2.9
作者：
Huang, Ling;Cai, Chen;Gu, Jun
通讯作者：
Gu, Jun
DOI：
10.1111/j.1432-1033.1988.tb13775.x
发表时间：
1988-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
KARPLUS, PA;KRAUTHSIEGEL, RL;SCHULZ, GE
通讯作者：
SCHULZ, GE
影响因子：
7.3
作者：
Seefeldt, T;Dwivedi, C;Guan, XM
通讯作者：
Guan, XM
影响因子：
4.6
作者：
Sun, Mengwei;Shi, Yi;Di Pasqua, Anthony J.
通讯作者：
Di Pasqua, Anthony J.
影响因子：
4.7
作者：
Xiao, Dong;Lew, Karen L.;Singh, Shivendra V.
通讯作者：
Singh, Shivendra V.