12种咪唑类离子液体对A549及HepG2细胞的增殖抑制作用

摘要

目的 考察咪唑类离子液体[C12mim]Cl、[C12mim]Br、[C12mim]PF6；[C10mim]Cl、[C10mim]Br、[C10mim]PF6；[C8mim]Cl、[C8mim]Br、[C8mim]PF6；[C6mim]Cl、[C6mim]Br、[C6mim]PF6体外对非小细胞肺癌A549及肝癌HepG2细胞的增殖抑制作用.方法 磺酰罗丹明B比色法检测咪唑类离子液体对A549及HepG2细胞的增殖抑制作用,以阳离子烷基链长度及阴离子种类分析构效关系.结果1.25～40 μmol/L离子液体阳离子咪唑环N-3位烷基链为6个碳,阴离子为Cl-、Br-和PF6-的咪唑类离子液体对A549细胞的生长均无明显影响,对HepG2细胞的生长有一定抑制作用,但最大浓度为40μmol/L作用72 h,抑制作用也未达50％；而N-3位烷基链为8、10、12个碳,阴离子为Cl-、Br-和PF6-的咪唑类离子液体,对A549和HepG2细胞的生长均有明显抑制作用(P＜0.05),呈明显的时效和量效关系,咪唑类离子液体对HepG2细胞的敏感性高于A549细胞.构效关系表明,N-3位烷基链的碳原子数是决定咪唑类离子液体抗肿瘤活性的关键,碳原子数越多,抗肿瘤活性越强,而阴离子的类型如C1-、Br-和PF6-对咪唑类离子液体的抗肿瘤活性影响不明显.结论 咪唑类离子液体阳离子N-3位烷基链长度＞6时能明显抑制A549和HepG2细胞生长,而阴离子种类不影响其抗肿瘤活性.%Objective To investigate the inhibitory effect of 12 imidazolium-based ionic liquids on the proliferation of non-small-cell lung cancer cell (A549) and hepatocellular carcinoma cell(HepG2) in vitro, and to analyze the structure-activity relationship. Methods Sulforho-damine B assay was used to examine the inhibition effect of these imidazolium-based ionic liquids against A549 cells and HepG2 cells. The structure-activity relationship was analyzed with the chain lengths of alkyl substitution at N-3 position of imidazole ring and the types of the anion species. Results When the chain length of alkyl substitution at N-3 position of imidazole ring was 6 for 1.25～40 μmol/L ionic liquids, and the anion were Cl-, Br- or PF-6, the anti-tumor activity had nearly no effect on proliferation of A549 cells, but had some inhibition effect on HepG2. The effect was still 50% below the peak of 40 μmol/L after 72 h. When the chain length of alkyl substitution at N-3 position of imidazole ring were 8, 10 or 12, and the anion were Cl-, Br- or PF-6, the anti-tumor activity against A549 cells and HepG2 cells was significant (P <0.05), and there was time-activity and does-activity relationship. The sensitivity of HepG2 cells was higher than that of A549 cells. The structure-activity relationship analysis revealed that the chain length of alkyl substitution at N-3 position of imidazole ring played a significant role in anti-tumor activity of these ionic liquids, and the larger the number of carbon atoms they had, the more activity they exerted. The inhibitory effect with different types of the anion species showed no obvious differences. Conclusion When the ionic liquids with the chain length of alkyl substitution at N-3 position of imidazole ring is more than 6 it has obvious anti-tumor activity against A549 cells and HepG2 cells in vitro, but the anion species has no effect in anti-tumor activity.