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.