Laboratory of Synthetic Chemistry, SAIC-Frederick Inc., National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):581-5. doi: 10.1016/j.bmcl.2009.11.085. Epub 2009 Nov 22.
The anti-cancer activity and cytotoxicity of imidazolium-based ionic liquids has been determined for the first time via NCI's in vitro 60 human tumor cell lines. The preliminary SAR showed that the chain length of alkyl substitution at N-3 position of imidazole ring plays crucial role towards anti-tumor activity and cytotoxicity of these ionic liquids. The ionic liquids with alkyl substitution of C-12 chain length were found to be effective against all 60 tumor cell lines and show very low cytotoxicity in most of the cases. Further increase in chain length resulted in enhanced growth inhibition of tumor cell lines as well as high cytotoxicity. Interestingly, active compounds 1-dodecyl-3-methylimidazolium chloride (8), 1-dodecyl-3-methylimidazolium tetrafluoroborate (9), 1-hexadecyl-3-methylimidazoium chloride (10), 1-octadecyl-3-methylimidazolium chloride (11), 1-octadecyl-3-methylimidazolium hexafluorophosphate (12), 1-octadecyl-3-methylimidazolium bis(triflic)imide (13) and 1-octadecyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate (14) were highly active against leukemia cell lines, especially compounds 13 and 14 where the cytotoxicity was also very low as given by LC(50) >100microM in all six leukemia cell lines.
首次通过 NCI 的体外 60 个人类肿瘤细胞系测定了基于咪唑鎓的离子液体的抗癌活性和细胞毒性。初步 SAR 表明，咪唑环 N-3 位上的烷基取代链长对这些离子液体的抗肿瘤活性和细胞毒性起着至关重要的作用。具有 C-12 链长烷基取代的离子液体被发现对所有 60 种肿瘤细胞系有效，并且在大多数情况下显示出非常低的细胞毒性。进一步增加链长会导致肿瘤细胞系的生长抑制增强以及细胞毒性增加。有趣的是，活性化合物 1-十二烷基-3-甲基咪唑鎓氯化物（8）、1-十二烷基-3-甲基咪唑鎓四氟硼酸盐（9）、1-十六烷基-3-甲基咪唑鎓氯化物（10）、1-十八烷基-3-甲基咪唑鎓氯化物（11）、1-十八烷基-3-甲基咪唑鎓六氟磷酸盐（12）、1-十八烷基-3-甲基咪唑鎓双（三氟甲磺酰基）亚胺（13）和 1-十八烷基-3-甲基咪唑鎓三（五氟乙基）三氟磷酸盐（14）对白血病细胞系具有很高的活性，特别是化合物 13 和 14，其在所有六种白血病细胞系中的细胞毒性也非常低，LC(50)>100μM。
