互叶白千层化学成分及其抗肿瘤活性研究

Chemical constituents of Melaleuca alternifolia and its antitumor activities

目的研究互叶白千层Melaleuca alternifolia茎皮中的化学成分及其抗肿瘤活性。方法采用硅胶柱色谱、凝胶柱色谱、重结晶、高效制备液相色谱法等现代分离方法和技术对其化学成分进行分离纯化,并根据理化性质和波谱数据进行结构鉴定。采用CCK-8法,以人非小细胞肺癌PC-9细胞、人结直肠腺癌HT-29细胞、人乳腺癌MCF-7细胞为模型,对所分离鉴定的部分化合物进行初步的体外细胞毒活性评价。结果从互叶白千层茎皮中分离得到11个化合物,分别鉴定为乌苏酸-3-O-β-顺式-咖啡酸酯(1)、乌苏酸-3-O-β-反式-咖啡酸酯(2)、阿魏酸三十酯(3)、3-O-乙酰基-11(12)-烯-乌苏-28,13β-二酯(4)、3-O-乙酰基乌苏酸(5)、咖啡酸三十酯(6)、乌苏酸(7)、正二十九烷醇(8)、乌苏-12(13)-烯-3-酮-28-羧酸(9)、3β-O-乙酰基-11α,12α-环氧-齐墩果烷-28,13β-内酯(10)、白桦脂醇(11)。结论化合物1与2互为顺反异构体,为首次从天然产物中分离得到的新化合物;除化合物11外,其余化合物均为首次从该植物中分离得到;化合物1的细胞毒活性较其异构体(2)强,对3种肿瘤细胞增殖具有中等强度的抑制作用。

Objective To investigate the chemical constituents of the barks and stems of Melaleuca alternifolia and its antitumor activities. Methods The chemical constituents were separated and purified consecutively by silica gel, Sephadex LH-20 column chromatography, recrystallization as well as preparative HPLC. Their structures were determined by physicochemical properties and spectral analyses. Furthermore, the cytotoxicity of some compounds against PC-9(human non-small cell lung cancer cell line), HT29(human colon cancer cell line) and MCF-7(human breast cancer cell line) were tested by CCK8 method. Results Eleven compounds were isolated and identified as ursolic acid 3-O-β-cis-caffeate(1), ursolic acid 3-O-β-trans-caffeate(2), tricontyl ferulates(3), 3-O-acetyl-11(12)-en-urs-28,13β-olide(4), 3-O-acetyl-ursolic acid(5), tricontyl caffeate(6), ursolic acid(7), n-nonacosanol(8), urs-12(13)-en-3-one-28-oic acid(9), 3β-O-acetyl-11α,12α-epoxy-oleanane-28,13β-olide(10), and betulin(11). Conclusion Compound 1 and 2 are cis-trans isomers. Compound 1 is isolated from natural product for the first time, all the compounds are isolated from this plant for the first time except for compound 11. Compound 1 exhibited moderate inhibited effect on the proliferation of three human cancer cell lines.