JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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In vitro antitumor activity of novel benzimidazole-based Cu(II) complexes.

Four benzimidazole-based Cu(II) complexes: Cu2 (p-2-bmp)2 Br4 (1), Cu2 (p-2-bmp)2 Cl4 (2), Cu2 (p-2-bmb)2 (DMF)2 Br4 ·(CHCl3 ) (3), and Cu(p-2-bmb)(NO3 )2 ·(CHCl3 ) (4) were isolated and characterized, where p-2-bmp is 1-((2-(pyridine-2-yl)-1H-benzoimidazol-1-yl)methyl)-1H-pyridine and p-2-bmb is 1-((2-(pyridin-2-yl)-1-benzoimidazol-1-yl)methyl)-1H-benzotriazole. Complexes 1 and 2 have binuclear configurations, 3 has a mononuclear structure, and 4has a one-dimensional (1-D) chain skeleton. To evaluate their potential anticancer effects on human carcinoma cells, anti-proliferation, DNA binding and cleavage, and apoptosis elicitation were examined. Compared with complexes 2, 3, and 4, complex 1 exhibited potent in vitro cytotoxicity toward four cell lines (MCF7, EC109, SH-SY5Y and QBC939), with SH-SY5Y cells demonstrating the most sensitivity. Therefore, further in-depth investigations were performed using complex 1. Absorption titration experiments, circular dichroism spectroscopic studies, and ethidium bromide displacement assays suggested that complex 1 binds to DNA through intercalation, significantly cleaves supercoiled pBR322 DNA, and inhibits DNA transcription. Cell cycle analysis revealed that SH-SY5Y cells were arrested in the G2/M phase after treatment with complex 1. Membrane permeability analysis and nuclear staining of SH-SY5Y cells showed that complex 1 could induce apoptosis.

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