Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline

Zhang,Zhen; Wang,Huiyun; Wang,Qibao; Yan,Maocai; Wang,Huannan; Bi,Caifeng; Sun,Shanshan; Fan,Yuhua

doi:10.3892/ijo.2016.3542

Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline

Authors:
- Zhen Zhang
- Huiyun Wang
- Qibao Wang
- Maocai Yan
- Huannan Wang
- Caifeng Bi
- Shanshan Sun
- Yuhua Fan
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Affiliations: School of Pharmacy, Jining Medical University, Rizhao, Shandong 276800, P.R. China, Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, Shandong 266100, P.R. China
Published online on: May 27, 2016 https://doi.org/10.3892/ijo.2016.3542
Pages: 691-699

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Abstract

Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit cancer-special proteasome and induce cell death in human cancer cells. However, the involved molecular mechanism is not known yet. We therefore synthesized three copper complexes and investigated their abilities on inhibiting proteasome activity and inducting apoptosis in human breast cancer cells. Furthermore, we employed molecular dockings to analyze the possible interaction between the synthetic copper complexes and the β5 subunit of proteasome which only reflects the chymotrypsin-like activity. Our results demonstrate that three Cu(II) complexes possess potent proteasome inhibition capability in a dose-dependent and time-dependent manner in MDA-MB-231 human breast cancer cells. They could bind to the β5 subunit of the 20S proteasome, which consequently cause deactivation of the proteasome and tumor cell death. The present study is significant for providing important theoretical basis for design and synthesis of anticancer drugs with low toxicity, high efficiency and high selectivity.

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