番荔枝皮化学成分及其抗肿瘤活性的研究

Constituents from the bark of Annona squamosa and their anti-tumor activity

目的:研究番荔枝Annona squamosa的化学成分,并对分离化合物进行活性筛选。方法:综合运用各种色谱方法分离纯化番荔枝中的化学成分;采用NMR等波谱方法鉴定其结构;运用SRB法测定化合物对肿瘤细胞体外增殖能力的抑制作用。结果:从番荔枝皮乙醇提取物中分离得到11个化合物,分别是annosquamosin C(1),15,16-epoxy-17-hydroxy-ent-kau-ran-19-oic acid(2),16,17-dihydroxy-ent-kauran-19-oic acid(3),annosquamosin A(4),ent-kaur-16-en-19-oic acid(5),19-nor-ent-kauran-4-ol-17-oic acid(6),16-hydroxy-ent-kau-ran-19-oic acid(7),ent-15β-hydroxy-kaur-16-en-19-oic acid(8),annosquamosin B(9),ent-16β,17-dihydroxykauran-19-al(10),16,17-dihydroxy-ent-kauran-19-oic acid methyl ester(11)。抗肿瘤活性实验表明,化合物1,2,3,5,9对人肺癌95-D细胞的体外增殖能力均具有不同程度的抑制作用,化合物5的活性最强,IC50为7.78μmol.L-1;化合物2,5,9对人卵巢癌A2780细胞有抑制作用,其中化合物2和9的抑制作用较强,IC50分别为0.89,3.10μmol.L-1。结论:化合物2,8,11分别为首次从该科、该属和该种植物分离得到;化合物5对人肺癌95-D细胞的抑制作用较强;化合物2和9对人卵巢癌细胞A2780的抑制作用较强。

Objective ： To investigate the constituents of the Annona squamosa and evaluate their anti-tumor activity. Method： The compounds were isolated and purified by various column chromatography. Their structures were elucidated by spectral data analysis. Their anti-tumor activity was assayed by SRB method. Result： Eleven compounds were obtained from the 95% EtOH extract. The structures were determined as ： annosquamosin C （ 1 ）, 15, 16-epoxy-17-hydroxy-ent-kau-ran-19-oic acid （2）, 16,17-dihydroxy-ent-kauran-19-oic acid （3） , annosquamosin A （4）, ent-kaur-16-en-19-oic acid （5）, 19-nor-ent-kauran-4-ol-17-oic acid （6）, 16-hydroxy ent-kan ran-19-oic acid （7）, ent-15fl-hydroxy-kaur-16-en-19-oic acid （ 8 ）, annosquamosin B （ 9 ）, ent-16fl, 17-dihydroxykauran-19-al （ 10 ）, 16, 17-dihydroxy-ent-kauran-19-oic acid me thyl ester （11）. Compounds 1,2,3,5,9 showed different inhibitory activities against 95-D lung cancer cells, the effect of compound 5 was strongest with the ICs0value 7.78 ~mol ~ L J ;Compounds 2,5,9 showed inhibitory ac- tivities against A2780 ovarian cancer cells ,the effects of compounds 2 and 9 were strong with the ICs0values being 0.89,3.10 ~mol ~ L-~ ,respectively. Conclusion： Compound 2 was firstly isolated from this family, while compound 8 and 10 were first found from this genus and the title species, respectively. The in vitro anti-tumor test showed compound 5 significantly inhibited 95-D lung cancer cells and compounds 2 and 9 exhibited remarkbale activity against A2780 ovarian cancer cells.