Antitumor and biological investigation of doubly cyclometalated ruthenium(II) organometallics derived from benzimidazolyl derivatives

作者：Elumalai Palani; Jeong Yong Joon; Park Dae Won; Kim Dong Hwan; Kim Hyunuk; Kang Se Chan; Chi Ki Whan

来源：Dalton Transactions, 2016, 45(15): 6667-6673.

DOI：10.1039/c5dt04400f

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.

• 出版日期2016