东京枫杨中三萜类化合物的分离鉴定与抗肿瘤活性

Isolation,identification and antitumor activity oftriterpenes from Pterocarya tonkinesis(Franch.)Dode.

目的阐明中国民间用于癌症治疗的中草药东京枫杨的抗癌活性成分。方法以细胞凋亡诱导、坏死性细胞毒活性为抗癌指标 ,采用硅胶、SephadexLH 2 0柱色谱、HPLC和流式细胞术 ,跟踪分离活性成分 ,利用理化手段鉴定化学结构 ;用SRB法及流式细胞术评价化合物的抗癌活性。结果从东京枫杨中分离鉴定了 3个具有抗癌活性的三萜类化合物齐墩果酸 (1)、2α ,3β ,2 3 三羟基齐墩果酸 (2 )和乌苏酸 (3) ,并对化合物 1～ 3和白桦酯酸 (4 )的抗癌活性进行了系统评价。化合物1～ 4在 10mg/L浓度下对K5 6 2细胞增殖的的抑制率分别为 4 2 4 %、4 5 2 %、33 7%和 34 3%。流式细胞术检测表明 :化合物 3对tsFT2 10细胞有细胞周期抑制和细胞凋亡诱导作用。结论化合物 1～

Aim To explore the anticancer components of Pterocarya tonkinesis(Franch.)Dode.,a Chinese folk medicine used in the treatment of some cancers.Methods The separation procedure was guided by a bioassay using tsFT210 cells,and the vacuum liquid column chromatography over silica gel,open column chromatography over Sephadex LH-20,and the preparative reversed phase HPLC were employed for the isolation and purification of the aimed bioactive constituents.The chemical structures were investigated by the spectroscopic method,and the biological activities were assayed by the SRB method and flow cytometry.Results Three pentacyclic triterpenes,arjunolic acid(1),oleanolic acid(2)and ursolic acid(3),were isolated from P.tonkinesis(Franch.)Dode.for the first time and identified.The biological effect of 1～2 and betulinic acid(4)which was previously isolated from the same plant were evaluated using mammalian cancer cell lines,tsFT210 and K562.Compounds 1～4 all inhibited the proliferation of K562 cells with the inhibition rates of 42.4%,45.2%,33.7% and 34.3% at 10 mg/L,respectively,and the IC_(50) value for compound 2 was (13.6 mg/L).Meanwhile,compound 3 induced apoptosis in tsFT210 cells at the concentrations over (30 mg/L).Conclusion Compounds 1～2 were isolated from the genus Pterocarya for the first time.It is also for the first time that pentacyclic triterpenes 1～4 were identified as the anticancer constituents of P.tonkinesis(Franch.)Dode.