2-二茂铁基乙醇的合成及其抗肿瘤活性

Synthesis and anti-tumor activity evaluation of 2-ferrocenylethanol

二茂铁与乙酸酐发生Friedel-Crafts酰基化反应制得了乙酰基二茂铁,接着通过Willgerodt-Kindler反应制得二茂铁乙酸,再经过还原反应得到了目标化合物2-二茂铁基乙醇。考察了反应条件对二茂铁乙酸还原成2-二茂铁基乙醇收率的影响。在还原剂为氢化铝锂、溶剂为四氢呋喃、n(氢化铝锂)∶n(二茂铁乙酸)=8∶1,反应温度为25℃,反应时间为24 h的最佳还原条件下,2-二茂铁基乙醇的收率为82%。体外活性测试结果表明,2-二茂铁基乙醇对人乳腺癌细胞MCF-7和MDA-MB-231、人肝癌细胞Hep G2、人宫颈癌细胞HeLa均有明显的抑制活性,其半数抑制浓度(IC50)分别为17.4、12.9、20.7、24.6μmol/L;此外,2-二茂铁基乙醇对人正常乳腺上皮细胞MCF-10A没有毒性,而阳性对照药物5-氟尿嘧啶展现出了一定的毒性。

Acetyl ferrocene was prepared by Friedel-Grafts acylation reaction between ferrocene and acetic anhydride.Then,ferrocenylacetic acid was synthesized by Willgerodt-Kindler reaction of acetyl ferrocene.Target compound 2-ferrocenylethanol was obtained by reduction reaction of ferrocenylacetic acid.The effects of reaction conditions on the yield of 2-ferrocenylethanol from ferrocenylacetic acid were studied.Under the optimum conditions of lithium aluminum hydride as reducing agent,tetrahydrofuran as solvent,n(lithium aluminum hydride)∶n(ferrocenylacetic acid)=8∶1,reaction temperature of 25℃,and reaction time of 24 h,the yield of 2-ferrocenylethanol was 82%.The in vitro activity test results showed that 2-ferrocenylethanol had obvious inhibitory activities against human breast cancer cells MCF-7 and MDA-MB-231,human liver cancer cells Hep G2,human cervical cancer cells HeLa,and the corresponding half inhibitory concentration(IC50)values were 17.4,12.9,20.7,24.6μmol/L,respectively.Additionally,2-ferrocenylethanol was nontoxic to human normal mammary epithelial cells MCF-10A,while the positive control drug 5-fluorouracil exhibited essential toxicity.