苯并咪唑
体外
吡啶
组合化学
化学
DNA
计算生物学
生物化学
立体化学
生物
药物化学
有机化学
作者
Jiyong Hu,Chunli Liao,Ruina Mao,Junshuai Zhang,Jin’an Zhao,Zhenzhen Gu
出处
期刊:MedChemComm
[The Royal Society of Chemistry]
日期:2017-12-28
卷期号:9 (2): 337-343
被引量:18
摘要
Copper is an essential element and has redox potential, thus copper complexes have been developed rapidly with the hope of curing cancer. To further develop anticancer agents and investigate their anticancer mechanisms, two Cu complexes, [Cu(bpbb)0.5·Cl·SCN]·(CH3OH) (1) and [Cu2(bpbb)·Br3·(OH)] n (2), were synthesized and characterized using 4,4'-bis((2-(pyridin-2-yl)-1H-benzo[d]imidazol-1-yl)methyl)biphenyl (bpbb), with associated Cu(ii) salts. Complex 1 is a binuclear structure, whereas 2 is a one-dimensional complex. Compared with 2, complex 1 exhibited potent in vitro cytotoxicity toward four cell lines (HCT116, BGC823, HT29, and SMMC7721), and was most effective against HCT116 cells. Therefore, further in-depth investigation was carried out using complex 1. Absorption spectral titration experiments, ethidium bromide displacement assays, and circular dichroism spectroscopic studies suggested that complex 1 binds strongly to DNA by intercalation. Complex 1 exhibited a clear concentration-dependent pBR322 DNA cleavage activity. Inductively coupled plasma mass spectrometry testing implied that complex 1 could enter cells and that DNA was one important target. Cellular level assays suggested that complex 1 activates the generation of intracellular reactive oxygen species, causing DNA damage, promoting cell cycle arrest and mitochondria dysfunction, and inducing cellular apoptosis.
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