Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half-sandwich Ruthenium(II) Complexes [RuX((6)-arene)(C5H4N-2-CH=N-Ar)](+)

摘要

New complexes [((6)-p-cymene)Ru(C5H4N-2-CH=N-Ar)X]PF6 [X = Br (1), I (2); Ar = 4-fluorophenyl (a), 4-chlorophenyl (b), 4-bromophenyl (c), 4-iodophenyl (d), 2,5-dichlorophenyl (e)] were prepared, as well as 3a-3e (X = Cl) and the new complexes [((6)-arene)RuCl(N-N)]PF6 (arene = C6H5OCH2CH2OH, N-N = 2,2-bipyridine (4), 2,6-(dimethylphenyl)-pyridin-2-yl-methylene amine (5), 2,6-(diisopropylphenyl)-pyridin-2-yl-methylene amine (6); arene = p-cymene, N-N = 4-(aminophenyl)-pyridin-2-yl-methylene amine (7)]. X-ray diffraction studies were performed for 1a, 1b, 1c, 1d, 2b, 5, and 7. Cytotoxicities of 1a-1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco-2) (IC50: 35.8-631.0 M), breast adenocarcinoma (MCF7) (IC50: 36.3-128.8.0 M), and hepatocellular carcinoma (HepG2) (IC50: 60.6-439.8 M), 3a-3e were tested against HepG2 and Caco-2, and 4-7 were tested against Caco-2. 1-7 were tested against non-cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5-fluorouracil (5-FU), but 3a-3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC50 than 5-FU. Complexes with X = Br or I had moderate activity against Caco-2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a, 2b, 3a, and 7 were tested against antibacterial susceptible and resistant Gram-negative and -positive bacteria. 1a, 2b, and 3a showed activity against methicillin-resistant S. aureus (MIC = 31-2000 gmL(-1)).