Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells
- 269 Downloads
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.
KeywordsChrysin Amino acid derivatives Apoptotic Anti-proliferative
We are grateful to the Construct Program of the Key Discipline in Hunan Province for financial support.
- Bender DM, Bao J, Dantzig AH, Diseroad WD, Law KL, Magnus NA, Peterson JA, Perkins EJ, Pu YJ, Reutzel-Edens SM, Remick DM, Starling JJ, Stephenson GA, Vaid RK, Zhang D, McCarthy JR (2009) Synthesis, crystallization, and biological evaluation of an orally active prodrug of gemcitabine. J Med Chem 52:6958–6961CrossRefPubMedGoogle Scholar
- Chiang JH, Yang JS, Ma CY, Yang MD, Huang HY, Hsia TC, Kuo HM, Wu PP, Lee TH, Chung JG (2011) Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol 24:20–29CrossRefPubMedGoogle Scholar
- Song XD, He J, Ma J, Liu YM, Zheng X, Lei XY, Guo Y (2014) Syntheses and anticancer activities of glycine derivatives of chrysin. Chem Res Chin Univ 35:1465–1470Google Scholar