大黄素衍生物的合成及其抑制白血病细胞增殖作用的研究

本研究探讨新合成的大黄素衍生物对白血病细胞增殖的抑制作用,希望从中筛选出具有抗白血病活性的药物,以备后续进行更深入的研究。通过对大黄素一系列的结构修饰合成10种大黄素衍生物,采用MTT比色法检测大黄素衍生物对多种白血病细胞株的增殖抑制作用。结果表明:大黄素衍生物E10-E19作用于K562细胞48 h的半数抑制浓度(IC50)为0.84-12.01μmol/L,其中大黄素衍生物E19的抑制增殖作用最强,E16、17对K562细胞没有抑制增殖作用。从中筛选出的E19作用于U937、NB4、Molt-4和CA-46细胞,其48 h IC50分别为0.85、0.9、0.76、0.8μmol/L。E19作用于LQ2细胞48 h的IC50为3.6μmol/L。E19作用于3例正常人外周血单个核细胞48 h的IC50为4.01-4.78μmol/L。结论:大黄素衍生物E19对白血病细胞增殖有显著的抑制作用,且具有一定特异性,对其抗白血病机的制值得进一步的研究。

Synthesis of Emodin Derivatives and Their Inhibiting Effects on Proliferation of Leukemia Cell Lines

The aim of this study was to explore the inhibitory effect of newly synthesised ernodin derivatives on the prolifaration of leukemia cell lines and to select the most effective one from these emodin derivatives for further resaerch. Emodin derivatives were synthesized by modifying the structure of emodin. MTT method was used to detect the proliferative inhibition in leukemia cell lines treated with emodin derivatives. The results showed that the half inhibitory concentration（ IC50 ）.for K562 cells treated with emodin derivatives El0 - 19 for 48 h was 0.84 - 12.01 μmol/L. El9 displayed the best anti-proliferative activity, while El6 and El7 did not show effects on K562 cells. Emodin derivative El9 was chosen for treating U937, NB4, Molt-4 and CA-46 cells, their IC50 for 48 h were 0.85, 0.9, 0.76, 0.8 μmol/L respectively. The IC50 of El9 for LQ2 cells was 3.60 μmol/L, and the IC50 range of E19 for normal human peripheral blood mononuclear cells at 48 h was 4.01 -4.78 μmol/L. It is concluded that emodin derivative E19 can strongly inhibit the growth of leukemia cells and its inhibiting effect on proliferation of leukemia cells has a certain specificity. The specific mechanism of E19 anti-leukemia effect should be further studied.