Lehrstuhl für Analytische Chemie, Ruhr-Universität Bochum, 44780 Bochum, Germany.
Biometals. 2011 Aug;24(4):645-61. doi: 10.1007/s10534-011-9414-9. Epub 2011 Jan 28.
The cytostatic properties of novel rhodium(III) thiacrown ether complexes RhCl(LL)([9]aneS(3)) with either aromatic κ(2)N ligands (n = 2) or anionic chelate ligands (n = 1) have been investigated for the human cancer cell lines HT-29 and MCF-7 and for immortalized HEK-293 cells. Taken together with literature IC(50) values for analogous complexes with polypyridyl ligands or 1,4-dithiane, the in vitro assays indicate that dicationic complexes with soft κ(2)N (imino) or κ(2)S (thiaether) ligands exhibit significantly higher antiproliferative effects than those with hard κ(2)N (amino) ligands. Dicationic complexes are more active than monocationic complexes with similar ligands. Pronounced apoptosis-inducing properties towards Jurkat cells were established for complexes with LL = bpm, dpq, and 1,4-dithiane. The order of activity (bpm > 1,4-dithiane > dpq > bpy) contrasts to that observed for adhesive cancer cells (bpm > bpy, 1,4-dithiane > dpq). Necrosis is insignificant in all cases. The percentage of Jurkat cells exhibiting apoptosis after 24 or 48 h incubation periods is directly correlated to the percentage of cells exhibiting high levels of reactive oxygen species. As established by online monitoring with a sensor chip system, treatment of MCF-7 cells with the bpm and 1,4-dithiane complexes leads to a significant and permanent concentration-dependent decrease in oxygen consumption and cellular adhesion.
新型铑（III）硫代冠醚配合物RhCl(LL)([9]aneS(3))（其中 LL 为具有芳香性 κ(2)N 配体（n = 2）或阴离子螯合配体（n = 1））的细胞停滞特性已在人类癌细胞系 HT-29 和 MCF-7 以及永生化的 HEK-293 细胞中进行了研究。结合具有多吡啶配体或 1,4-二噻烷的类似配合物的文献 IC(50)值，体外测定表明，具有软 κ(2)N（亚氨基）或 κ(2)S（硫醚）配体的二价配合物比具有硬 κ(2)N（氨基）配体的二价配合物表现出更高的抗增殖作用。具有类似配体的二价配合物比单价配合物更具活性。对于具有 LL = bpm、dpq 和 1,4-二噻烷的配合物，已经确立了对 Jurkat 细胞具有明显的诱导凋亡作用。活性顺序（bpm > 1,4-二噻烷 > dpq > bpy）与在粘附癌细胞中观察到的活性顺序（bpm > bpy，1,4-二噻烷 > dpq）相反。在所有情况下，坏死都不明显。孵育 24 或 48 小时后，表现出凋亡的 Jurkat 细胞的百分比与表现出高水平活性氧的细胞的百分比直接相关。通过传感器芯片系统在线监测，用 bpm 和 1,4-二噻烷配合物处理 MCF-7 细胞会导致氧消耗和细胞粘附的浓度依赖性显著和永久性下降。
