三甲氧基没食子酸1,2,4-噻二唑-3,5-二酮衍生物的合成及其对HL60细胞增殖的抑制作用

Synthesis of 1,2,4-Thiadiazole-3,5-dione Derivatives of Trimethoxy GallicAcid and Its Inhibition of HL60 Cell Line Proliferation

合成了三甲氧基没食子酸1,2,4-噻二唑-3,5-二酮系列衍生物4a^4e,采用MTT法测定了中间产物2、3和目标化合物4a^4e对急性白血病HL60细胞增殖的抑制作用,并考察了4b和4c与阳性对照TDZD-8对HL60细胞增殖抑制的协同作用。结果表明:化合物2~4对HL60细胞增殖均有一定的抑制作用,其中化合物4b和4c抑制效果较好,半数抑制浓度(IC50)分别为10.60和6.31μmol/L;而TDZD-8对HL60细胞的IC50值为0.30μmol/L。此外,4b和4c协同TDZD-8对急性白血病细胞株HL60具有较好的增殖抑制作用,当4b和TDZD-8浓度分别为5.0和0.34μmol/L时,两者的协同抑制率为94.45%,协同指数CI值为0.58;当5c和TDZD-8浓度分别为5.0和0.34μmol/L时,两者的协同抑制率为98.76%,协同指数(CI)值为0.31。可以看出,新型没食子酸1,2,4-噻二唑-3,5-二酮衍生物具有作为治疗人急性白血病药物先导物的潜力。

A series of 1,2,4-thiadiazole-3,5-dione derivatives of trimethoxy gallic acid(4a-4e)were synthesized,and the intermediate products 2,3 and the target compounds 4a-4e were tested against the proliferation of acute leukemia HL60 by MTT method.The inhibition of cell proliferation,and the synergistic effects of 4b and 4c and the positive control TDZD-8 on the proliferation inhibition of HL60 cells were investigated.The results showed that compounds 2-4 had a certain inhibitory effect on the proliferation of HL60 cells.Among them,compounds 4b and 4c had better inhibitory effects,and their half inhibitory concentrations(IC50)were 10.60 and 6.31μmol/L,respectively and the IC50 value of TDZD-8 on HL60 cells was 0.30 mmol/L.In addition,4b and 4c cooperated with TDZD-8 had better proliferation inhibitory effect on the acute leukemia cell line HL60.When the concentrations of 4b and TDZD-8 were 5.0 and 0.34μmol/L,the synergistic inhibition rate of them was 94.45%,and the collaborative index(CI)value of the synergy index was 0.58;when the concentrations of 5c and TDZD-8 were 5.0 and 0.34μmol/L,the synergistic inhibition rate was 98.76%and the CI value was 0.31.It could be seen that the new gallic acid 1,2,4-thiadiazole-3,5-dione derivative could potentially act as the drug leader for treating human acute leukemia.