10.1021/acschembio.5b00708.s001
Baoxia Liang
Baoxia
Liang
Weiyan Shao
Weiyan
Shao
Cuige Zhu
Cuige
Zhu
Gesi Wen
Gesi
Wen
Xin Yue
Xin
Yue
Ruimin Wang
Ruimin
Wang
Junmin Quan
Junmin
Quan
Jun Du
Jun
Du
Xianzhang Bu
Xianzhang
Bu
Mitochondria-Targeted Approach: Remarkably Enhanced
Cellular Bioactivities of TPP2a as Selective Inhibitor and Probe toward
TrxR
American Chemical Society
2015
TPP 2a
cancer cell lines
Remarkably Enhanced Cellular Bioactivities
TrxR inhibitor 2
ROS
compound TPP 2a
subcellular mitochondrial TrxR
HeLa cancer cells
2015-12-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Mitochondria_Targeted_Approach_Remarkably_Enhanced_Cellular_Bioactivities_of_TPP2a_as_Selective_Inhibitor_and_Probe_toward_TrxR/2099737
A mitochondria-targeted
approach was developed to increase the
cellular bioactivities of thioredoxin reductase (TrxR) inhibitors.
By being conjugated with a triphenylphosphine (TPP) motif to a previously
found TrxR inhibitor 2a, the resulted compound TPP2a can target subcellular
mitochondria and efficiently inhibit cellular TrxR, leading to remarkably
increased cellular ROS level and mitochondrial apoptosis of HeLa cancer
cells. The cellular bioactivities of TPP2a, including its cytotoxicity
against a panel of cancer cell lines, dramatically elevated compared
with its parental compound 2a. The selectively and covalently interaction
of TPP2a with subcellular mitochondrial TrxR was validated by fluorescent
microscopy. Moreover, a nonspecific signal quenching coupled strategy
was proposed based on the environmentally sensitive fluorescence of
TPP2a, which makes it possible to label TrxR by removing the nonspecific
backgrounds caused by TPP2a under complex biosettings such as cellular
lysates and living cells, implicating a potential of TPP2a for TrxR-specific
labeling.