title: Synthesis and anti-tumor activity evaluation of Matijin-Su derivatives.
abstract: 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 20μM, and compound 1 and 3 showed an IC50 value of less than 9μM. 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.
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors.forename: Bixue
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Qiu
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China.
authors.forename: Peixue
authors.initials: P
authors.lastname: Cao
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Meifen
authors.initials: M
authors.lastname: Zhu
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: yfeng@hku.hk.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China. Electronic address: guangyi_liang@126.com.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; C000595690:N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol; D017382:Reactive Oxygen Species
keywords: Anti-tumor activity; Hepatocellular carcinoma; MTS derivatives; Synthesis