In this study,a total of 27 ARG(arctigenin)derivatives were designed,of which nine were novel deriv-atives targeting tumor cell mitochondria.Biological studies showed that all the triphenylphosphine conjugated compounds had a significant increase in anti-tumor activity compared with ARG.Among them,Mito-ARG-7 showed a high selectivity against A549 cells,and its anti-tumor activity was increased by 86.38％compared with ARG.This study showed that the anti-tumor mechanisms of Mito-ARG-7 included significantly increasing the production of reactive oxygen species in A549 cells,causing a decrease in mitochondrial membrane potential,promoting the release of apoptotic protein Cytochrome C from mitochondria to cytoplasm in the endogenous mitochondrial apoptosis signaling pathway,and causing the activation of Caspase family proteins to eventually induce the apoptosis of tumor cells.The novel arctigenin derivative with mito-chondrial targeting function synthesized in this study provides a reference for the development of targeted anti-tumor drugs.
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