1,8-二羟基-3-乙酰基-6-甲基-9,10蒽醌的合成及对卵巢癌细胞的生长抑制

目的:合成1,8-二羟基-3-乙酰基-6-甲基-9,10蒽醌,探讨该合成产物对人卵巢癌细胞(SKOV3)的生长抑制作用。方法:以大黄素为基础结构,化学全合成1,8-二羟基-3-乙酰基-6-甲基-9,10蒽醌;构建SKOV3与人脐静脉血管内皮细胞(HUVEC)的交换培养液条件共培养体系,以卡铂为对照药,MTT法检测合成产物对单独培养SKOV3和HUVEC的半数抑制浓度(IC50)及条件共培养体系中两种细胞的IC50。结果:化合物结构经IR,1H-NMR和13C-NMR确证。合成产物和卡铂对单独培养SKOV3的IC50分别为111.72,177.63μmol·L-1,对单独培养HUVEC的IC50分别为198.11,131.53μmol·L-1;合成产物和卡铂对条件共培养体系中SKOV3的IC50分别为104.48,180.7μmol·L-1,对HUVEC的IC50分别为239.22,178.62μmol·L-1。结论:1,8-二羟基-3-乙酰基-6-甲基-9,10蒽醌显示出比卡铂更为优越的抑制卵巢癌细胞生长活性;合成产物对单独培养和条件培养基共培养细胞的IC50值不同,反映了单细胞体系与条件培养基共培养体系在药物筛选结果上的差异。

Synthesis of 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone and its inhibition effect on ovarian carcinoma cells SKOV3

Objective:To synthesize 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone and observe its inhibition effect on ovarian carcinoma cells SKOV3.Methods:1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone was synthesized from emodin,and its structure was identified by IR,1H-NMR and 13C-NMR spectra.MTT assay was used to determine the IC50s of 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone and carboplatin against SKOV3 and HUVEC cells in the single cell system or the condition medium of co-culture cell system,respectively.Results:The structure of 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone was confirmed by IR,1H-NMR and 13C-NMR.In the single cell system,the IC50s of the synthetic product and carboplatin were 111.72 and 177.63μmol·L-1 against SKOV3 cells,and 198.11 and 131.53μmol·L-1 against HUVEC cells,respectively.In the condition medium of co-culture system,the IC50s of the synthetic product and carboplatin were 104.48 and 180.7μmol·L-1 against SKOV3 cells,and 239.22 and 178.62μmol·L-1 against HUVEC cells,respectively.Conclusion:Compare with carboplatin,1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone shows stronger antiproliferative activity against SKOV3 cells in the condition medium of co-culture system.There is difference in the drug screening result between the single cell system and the condition medium of co-culture cells system.