Journal
DALTON TRANSACTIONS
Volume 45, Issue 15, Pages 6667-6673Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5dt04400f
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Funding
- Basic Science Research program through the National Research Foundation of Korea - Ministry of Science, ICT and Future Planning [NRF-2013R1A1A2006859]
- Ministry of Education [NRF-2014R1A1A2007828]
- Priority Research Centers program through the NRF [2009-0093818]
- Research and Development Program of the Korea Institute of Energy Research (KIER) [B6-2484]
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In this study, we report the synthesis, anticancer and biological properties of three doubly cyclometalated phenylbenzimidazole derived ruthenium(II) organometallics (1-3) and their corresponding three organic ligands. The structures of 1-3 were fully characterized by various analytical techniques, and the meso stereoisomer of the doubly cyclometalated ruthenacycle 3 was unambiguously confirmed by single crystal X-ray diffraction. The anticancer effects of the newly synthesized compounds were tested against selected human cancer cell lines AGS (gastric carcinoma), SK-hep-1 (hepatocellular carcinoma), and HCT-15 (colorectal carcinoma). The growth inhibitory effects of ruthenacycles 1-3 on cancer cells were found to be considerably more effective against the abovementioned cancer cells than the reference drug oxaliplatin. Compound 2 exhibited a more specific effect on the AGS cells. Gene-fishing and ELISA array were performed to analyze the target genes and cytokine secretion by 2. As a result, a significant reduction was observed in RPS21 by 2. Moreover, 2 increased the secretion of cytokines such as IFN. in macrophages and reduced the release of cytokines such as rantes and IGF-1. These results show that 2 could be a very good anticancer drug through the regulation of the RPS21 gene and cytokines.
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