title: Zinc(II) complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers that trigger DNA damage-mediated p53 phosphorylation in cancer cells.
abstract: In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and [Zn(bpbp)2](ClO4)2·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.
authors: Department of Chemistry, Jinan University, Guangzhou, 510632, PR China.
authors: Shenggui
authors: S
authors: Liu
authors: Wenqiang
authors: W
authors: Cao
authors: Lianling
authors: L
authors: Yu
authors: Wenjie
authors: W
authors: Zheng
authors: Linlin
authors: L
authors: Li
authors: Cundong
authors: C
authors: Fan
authors: Tianfeng
authors: T
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004249:DNA Damage / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D010766:Phosphorylation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056831:Coordination Complexes; D016159:Tumor Suppressor Protein p53; C009712:bis-benzimidazole; D015032:Zinc