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

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.