Synthesis and anti-tumor activity evaluation of Matijin-Su derivatives

•A series of dipeptides was synthesized and evaluated for anti-tumor activities.•The IC50 of compounds 1, 3, 4, 11, 13 were less than 20 μM.•Compounds 1 and 3 showed significantly inhibition on HepG2 and PLC/PRF/5 cell.•Compounds 1 and 3 could induce production of intracellular ROS.•Compounds 1 and 3 could retard HepG2 cells from G1/S transition and proliferation.

A series of Matijin-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l-phenylalanol) derivatives was synthesized and evaluated for their anti-tumor activities in hepatocellular carcinoma cells. The IC50 of compounds 1, 3, 4, 11, 13 were less than 20 μM, and compound 1 and 3 showed an IC50 value of less than 9 μM. Expansion inhibition could be found significantly in compound 1 and 3-treated human hepatoma cell HepG2 and PLC/PRF/5, while both compounds exhibit lower toxicity to human hepatocyte cell line L-02. Compound 1 and 3 could induce cell cycle arrest at G1/S phase. This may be attributed to increase level of intracellular reactive oxygen species (ROS). Up-regulation of p38 MAPK activity in responding the ROS stabilize p53 and activate p21 transcription, the critical regulatory in G1/S checkpoint. Observations in this study shed light on the potential of MTS derivatives compound 1 and 3 as novel suppressors to human liver cancer.

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