Selenium electrophilic center shuttles active electrons to boost mitochondrial electron leakage
Junping Wang, Mingkai Chen, Yuanyuan You, Junxian Guo, Fei Cai, Fen Pi, Li Ma, Tianfeng Chen
Abstract
Designing drugs based on the high level of redox homeostasis characteristics is a viable approach to reduce the side effects of chemotherapeutic drugs. Previous strategies mainly focused on increasing oxidative stress or inhibiting antioxidant systems. Herein, we report on a new strategy to design efficient chemotherapeutics by employing an electrophilic center to convert antioxidant agents to oxidizing stress. By employing a strong polarization selenium atom (Se), we constructed an electrophilic center with "easy in easy out" characteristics to shuttle active electrons from NADH and GSH to boost mitochondrial electron leakage. The experimental results confirmed that the electrophilic center shuttles electrons through Se radical intermediates, and the polarizability strength of the center is critical for electron-shuttle efficiency. The strategy of constructing electrophilic centers with strong polarization properties to intelligently regulate active electrons has opened new avenues for the development of chemotherapy drugs and will also have broad applications in biological and medical fields.