Department of Chemistry, Jinan University, Guangzhou, 510632, PR China.
Dalton Trans. 2013 Apr 28;42(16):5932-40. doi: 10.1039/c3dt33077j.
In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and Zn(bpbp)22·CH3CH2OH·H2O (2) (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex 2 demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 μM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex 2 was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex 2 was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(II) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.
在本研究中，设计、合成了两种含有双苯并咪唑衍生物的锌（II）配合物，Zn(bpbp)Cl2（1）和Zn(bpbp)22·CH3CH2OH·H2O（2）（bpbp=2,6-双（1-苯基-1H-苯并[d]咪唑-2-基）吡啶），并评估了它们的体外抗癌活性。还阐明了它们导致癌细胞死亡的潜在分子机制。通过与顺铂比较，这些配合物被鉴定为对五种人癌细胞系具有很强的增殖抑制作用。与顺铂相比，配合物 2 对 MCF-7 人乳腺癌细胞的生长抑制具有剂量依赖性，IC50 为 2.9 μM。尽管具有这种功效，但这些配合物在人癌细胞和正常细胞之间具有很大的选择性。配合物 2 诱导 MCF-7 细胞凋亡的证据是亚 G1 细胞群的积累、DNA 片段化和核浓缩。对细胞内机制的进一步研究表明，配合物 2 通过触发 DNA 损伤能够诱导 p53 依赖性的癌细胞凋亡。基于这些证据，我们认为含有双苯并咪唑衍生物的锌（II）配合物可能是作为人类癌症化疗药物进一步评估的候选物。
