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Medicinal Chemistry Research

, Volume 24, Issue 5, pp 1789–1798 | Cite as

Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells

  • Xiudao Song
  • Yunmei LiuEmail author
  • Jin Ma
  • Jun He
  • Xing Zheng
  • Xiaoyong Lei
  • Guorong Jiang
  • Lurong Zhang
Original Research

Abstract

Two series of amino acid derivatives containing chrysin were prepared from 7-O-carboxymethyl chrysin (4a) and 7-O-carboxypropyl chrysin (4b) and amino acid methyl esters by treatment with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxybenzotriazole as coupling reagents. The anti-proliferative activities of these derivatives in vitro against human gastric carcinoma MGC-803 cells were evaluated by the standard MTT method. The results showed that among these derivatives tested, compound N-[4-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)butyryl]-l-isoleucine methyl ester (7c) exhibited the most potent inhibitory activity against the growth of MGC-803 cells with IC50 value of 3.78 μmol/L, comparable to the positive control cisplatin. The preliminary apoptotic mechanism of compound 7c was also investigated by flow cytometry (FCM) and Western blot analysis. Results form the FCM assay demonstrated that compound 7c could induce the apoptosis of MGC-803 cells in a dose-dependent manner. And further Western blot assay indicated that 7c could induce the apoptosis through increasing protein expression of Bax and decreasing protein expression of Bcl-xl. In summary, these results suggest that compound 7c may serve as an effective chemotherapeutic candidate.

Keywords

Chrysin Amino acid derivatives Apoptotic Anti-proliferative 

Notes

Acknowledgments

We are grateful to the Construct Program of the Key Discipline in Hunan Province for financial support.

Supplementary material

44_2014_1267_MOESM1_ESM.doc (46.8 mb)
Supplementary material 1 (DOC 47931 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiudao Song
    • 1
    • 2
  • Yunmei Liu
    • 1
    Email author
  • Jin Ma
    • 3
  • Jun He
    • 4
  • Xing Zheng
    • 1
  • Xiaoyong Lei
    • 1
  • Guorong Jiang
    • 2
  • Lurong Zhang
    • 2
  1. 1.Institute of Pharmacy & PharmacologyUniversity of South ChinaHengyangChina
  2. 2.Suzhou Academy of Wumen Chinese MedicineSuzhou Hospital of Traditional Chinese MedicineSuzhouChina
  3. 3.Soochow University Affiliated Children’s HospitalSuzhouChina
  4. 4.Institute of Chemistry & Chemical EngineeringUniversity of South ChinaHengyangChina

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