Designing Fluorescent Probes For Sensing Biothiols And Thiophenol,and Developing Xanthohumol-inspired Prooxidative Anticancer Agents

Fluorescent probes exhibit an excellent ability to sense biologically active molecules due to their high sensitivity,simple operation,low detection limit and biocompatibility.Biothiols,including glutathione(GSH),cysteine(Cys)and homocysteine(Hcy),are widely involved in maintaining redox homeostasis,signal transduction,drug metabolism and other physiological processes.Thiophenol is famous as an environmental pollutant and toxic substance in living organisms.Exposure to thiophenol can cause severe kidney and liver damage,central nervous system damage,and even death.Thus,developing fluorescent probes for monitoring biothiols and thiophenol is highly anticipated.Developing prooxidative anticancer agents to kill cancer cells by promoting generation of reactive oxygen species(ROS)to hit aberrant redox homeostasis observed in cancer cells has surfaced as an important anticancer strategy.However,how to improve the efficacy of prooxidative anticancer agents in generating ROS remains a challenge.The bottleneck could be solved by an organelle-targeted strategy,but there is very little research on developing natural product-inspired prooxidative anticancer agents based on this strategy.In this context,we designed fluorescent probes for sensing biothiols and thiophenol,and also developed xanthohumol-inspired prooxidative anticancer agents based on an organelle-targeted strategy.The main contents are summarized as follows:(1)We designed the probe HB-NBD,composed of the hemicyanine dye as the reporter and NBD as the response site of biothiols.The probe can selectively react with biothiol and exhibits the advantages of fast reaction speed and low detection limit.In addition,the probe was successfully used to imagine mitochondrial biothiols in HepG2 cells.(2)We developed the probe HS for monitoring thiophenol by using the hemicyanine dye as a fluorophore and the 2,4-nitrophenyl ether as a reactive group.The probe is capable of rapidly detecting thiophenol(10 min)with high selectivity and low detection limit(68 nM),also facilitating the naked-eye observation.Furthermore,the probe was successfully applied for detecting thiophenol in HepG2 cells.(3)Mitochondria are the energy powerhouse of the cell,but also the main site of intracellular ROS generation.Lysosome plays a regulatory role in cell metabolism as a digestive organ of cell.Using xanthophenol extracted from hops as a lead,we designed and synthesized its triphenylphosphonium-based mitochondria-targeted(Mito-XN)and morpholine-based lysosome-targeted(Lyso-XN)analogs as prooxidative anticancer agents for improving its efficacy in generating ROS and ability in killing selectively cancer cells.The related experiments are currently underway.