大黄素三甲氧基衍生物合成及体外抗肿瘤活性试验

Synthesis of trimethoxy derivatives of emdoin and its anti-tumor activities test in vitro

目的:以天然存在的大黄素为原料合成了甲基化衍生物三甲氧基大黄素,并进行体外抗肿瘤活性的研究。方法:利用硫酸二甲酯/丙酮甲基化组合合成目标化合物1,3,8-三甲氧基-6-甲基蒽醌;通过常规方法,对其理化性质进行鉴定。采用HPLC及ESI-MS对其结构进行表征;通过MTT比色法与流式细胞术检测其对K562细胞增殖及细胞周期分布的影响。结果:三甲氧基大黄素为淡黄色粉末,mp:226～227℃,溶于氯仿等有机溶剂。其结构经HPLC及ESI-MS检测得到确证;浓度依赖性地抑制K562细胞的增殖,并使G0/G1期的细胞比例增加。结论:以大黄素为原料,成功合成了其新的衍生物。三甲氧基大黄素具有抑制K562细胞增殖及阻滞细胞周期由G0/G1期向S期移行的抗肿瘤活性。

OBJECTIVE To synthesize emodin derivatives and evaluale its anti-tumor activities in vitro.METHODS A new emodin trimethoxy derivatives were synthesized from emodin with （Me）2 SO4. The physicochemical property of the new derivatives was identified with routine methods. And its structure was characterized by HPLC and ESI-MS spectra. The effect of the new derivatives on K562 cell proliferation was detected by MTT, as well as the cell cycle by flow cytometry. RESULTS Emod-in derivatives were slight yellow powder with mp.- 226 - 227 ℃, And its structure was confirmed by ESI-MS spectra and HPLC. The new derivatives could inhibit K562 cell proliferation in dose-dependent maxmer and arrest cell cycle in G0/G1. CON- CLUSION The new derivatives were synthesized from emodin successfully. The emodin derivatives had anti-tumor activities of K562 cell proliferation ildaibition and cell cycle arresting from G0/G1 to S phase.