Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, 66424 Homburg, Germany.
Bioorg Med Chem. 2012 Jul 15;20(14):4390-6. doi: 10.1016/j.bmc.2012.05.038. Epub 2012 May 24.
A series of novel CK2 inhibitors, tetrahalogenated benzimidazoles carrying an aminoalkylamino group at position 2, has been prepared by nucleophilic substitution of the respective 2,4,5,6,7-pentabromobenzimidazoles and 2-bromo-4,5,6,7-tetraiodobenzimidazoles. The new derivatives as well as some previously obtained tetrahalogenobenzimidazoles, including 4,5,6,7-tetrabromobenzimidazole (TBI) and 4,5,6,7-tetraiodobenzimidazole (TIBI), were evaluated for activity against the hormone-sensitive human prostate cancer cell line LNCaP. The activity of 2-aminoalkylamino derivatives was notably higher (LD(50) 4.75-9.37 μM) than that of TBI and TIBI (LD(50) ≈ 20 μM). The determination of the LD(50) value identified the 2-aminoethylamino-4,5,6,7-tetraiodobenzimidazole with an additional methyl group at position 1 (6) as the most efficient compound (LD(50): 4.75 ± 1.02 μM). Interestingly, there was no clear correlation between cell viability and apoptosis induction indicating additional cell death mechanisms.
一系列新型 CK2 抑制剂，即 2 位带有氨基烷基氨基取代基的四卤代苯并咪唑，通过相应的 2,4,5,6,7-五溴苯并咪唑和 2-溴-4,5,6,7-四碘苯并咪唑的亲核取代反应制备而成。新的衍生物以及一些之前获得的四卤代苯并咪唑，包括 4,5,6,7-四溴苯并咪唑（TBI）和 4,5,6,7-四碘苯并咪唑（TIBI），都对激素敏感的人前列腺癌细胞系 LNCaP 的活性进行了评估。2-氨基烷基氨基衍生物的活性明显更高（LD50 为 4.75-9.37 μM），而 TBI 和 TIBI 的活性则相当（LD50≈20 μM）。LD50 值的测定确定了 1 位带有额外甲基的 2-氨基乙基氨基-4,5,6,7-四碘苯并咪唑（6）为最有效的化合物（LD50：4.75±1.02 μM）。有趣的是，细胞活力和凋亡诱导之间没有明显的相关性，这表明存在其他细胞死亡机制。
