期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 20, 页码 7830-7835出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201916316
关键词
bioinorganic chemistry; copper-based drugs; glutathione; metallothionein; redox activity
资金
- Idex PhD grant (University of Strasbourg)
- Robert A. Welch Foundation [AT-1935-20170325]
- National Institute of General Medical Sciences (NIH) [R35G M128704]
- National Science Center of Poland (NCN) under Opus grant [2018/31/B/NZ1/00567]
Copper complexes are of medicinal and biological interest, including as anticancer drugs designed to cleave intracellular biomolecules by O-2 activation. To exhibit such activity, the copper complex must be redox active and resistant to dissociation. Metallothioneins (MTs) and glutathione (GSH) are abundant in the cytosol and nucleus. Because they are thiol-rich reducing molecules with high Cu-I affinity, they are potential competitors for a copper ion bound in a copper drug. Herein, we report the investigation of a panel of Cu-I/Cu-II complexes often used as drugs, with diverse coordination chemistries and redox potentials. We evaluated their catalytic activity in ascorbate oxidation based on redox cycling between Cu-I and Cu-II, as well as their resistance to dissociation or inactivation under cytosolically relevant concentrations of GSH and MT. O-2-activating Cu-I/Cu-II complexes for cytosolic/nuclear targets are generally not stable against the GSH/MT system, which creates a challenge for their future design.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据