(-)-antofine及其新型衍生物体外抗乳腺癌活性

Anti- breast cancer activity of (-)-antofine and its novel derivatives in vitro

目的研究(-)-antofine及其新型衍生物抗乳腺癌活性。方法以高藜芦酸和3-苄氧基大茴香醛为初始原料设计合成一系列新型(-)-antofine衍生物,经熔点、电喷雾电离质谱(ESR-MS)、氢核磁共振(1H-NMR)和碳核磁共振(13C-NMR)等方法表征后,通过四甲基偶氮唑盐比色法测定其对人乳腺癌细胞MCF-7和大鼠扩散乳腺癌细胞F3Ⅱ的半数抑制浓度(IC50),并与紫杉醇、母体(-)-antofine作对比。结果衍生物5a、5b、5c、5e、5f、5h对MCF-7细胞的IC50>0.9μmol.L-1,对F3Ⅱ细胞的IC50>0.7μmol.L-1,均大于紫杉醇和母体(-)-antofine的IC50。(-)-antofine衍生物5g对MCF-7细胞和F3Ⅱ细胞的IC50分别是[(0.41±0.02)、(0.32±0.04)μmol.L-1],与紫杉醇[(0.46±0.02)、(0.38±0.03)μmol.L-1])比较无显著差异(P>0.05);小于(-)-antofine[(0.62±0.01)、(0.57±0.02)μmol.L-1],比较有显著差异(P<0.05)。衍生物5d对MCF-7细胞和F3Ⅱ细胞的IC50分别是[(0.48±0.01)、(0.42±0.02)μmol.L-1],与紫杉醇的IC50比较无显著差异(P>0.05);小于(-)-antofine的IC50,比较有显著差异(P<0.05)。结论 (-)-antofine衍生物5d和5g表现出优良的体外抗乳腺癌活性,均优于母体(-)-antofine。

AIM To research the anti-breast cancer activity of （-）-antofine and its novel derivatives in vitro. METHODS A series of （-）-antofine derivatives were firstly designed and synthesized by the reaction of 3,4-dimethoxyphenylacetic acid and 3- （benzyloxy） anisal. Their structural information was extensively characterized by using melt point, ESR-MS, 1H-NMR and 13C-NMR. Then anti-breast cancer activity of （-）- antofine and its novel derivatives was also evaluated against two breast cancer cell lines （MCF-7, F3 11 ） in vitro by using an MTT-assay. RESULTS Compounds 5a, 5b, 5c, 5e, 5f, 5h exhibited moderate activity against MCF-7 cells with ICs0 〉 0.9 μmol·L^-1 and against F3 II cells ICso 〉 0.7 μmol·L^-1, which were higher than that of paclitaxel and （-）-antofine. The IC50 values of compound 5g were （（0.41 ± 0.02）, （0.32 ± 0.04） μmol·L^-1） and compound 5d were （（0.48 ± 0.01）, （0.42 ± 0.02）μmol·L^-1） against MCF-7 cells and F3 1 cells respectively, which were lower than that of （-）-antofine （（0.62 ± 0.01 ）, （0.57 ± 0.02） μmol·L^-1） （P 〈 0.05）. While comparing with paclitaxel （（0.46 ± 0.02）, （0.38 ± 0.03） μmol·L^-1）, compound 5g and 5d show no significant difference （P 〉 0.05）. CONCLUSION Compared with （-）-antofine, （-）-antofine derivatives 5d and 5g showed slightly better anti-breast cancer activity against MCF-7 cells and F3 11 cells.