Synthesis of Epigallocatechin Gallate Alkylated Derivatives and Their Anti-tumor Activity in Vitro

Objective: To design the synthesis of high epigallocatechin gallate（EGCG） alkylated derivatives,analyze the structure-activity relationship and the pharmacological activity in inhibiting human hepatocellular carcinoma cell proliferation,in order to select the more stable and effective EGCG derivatives.Method: With EGCG and （CH 3 CH 2 O） 2 SO 2 as raw materials,a series of EGCG derivatives were ethylated. The effect of ethylated EGCG on the proliferation of human hepatocellular carcinoma cell SMMC-7721 and Hep G2 were determined by 3-（4,5 dimethylthiazol-2-yl）-2,5 dimethyl-2H-tetrazolium bromide（MTT） method. With the cell density at 1 × 10 8 /mL,the 3/4 of EGCG derivatives were diluted into four concentrations,with 60,80,100,150 mg·L -1 ,and 30,40,50,60 mg·L -1 for SMMC-7721 cells,and 60,80,100,150 mg·L -1 ,and 20,30,40,50 mg·L -1 for Hep G2 cells,both were drug groups. A cell control group was also set up. Each concentration group has four complex wells,and the cells were continuously cultured for 24 h after addition of drugs. Result:We synthesized four EGCG derivatives. Their structures were identified by 1 H-NMR, 13 C-NMR, 2 DNMR,mass spectrometry and other methods,all of them were novel compounds. Ethylated EGCG product 3 and 4 can inhibit proliferation of hepatocellular carcinoma cell SMMC-7721 and Hep G2. Conclusion: Ethylated EGCG product 3 and4 have inhibition effect on hepatocellular carcinoma cell SMMC-7721 and Hep G2,and 4 has a much stronger effect than EGCG.