Studies of ruthenium(II) polypyridyl complexes on cytotoxicity in vitro, apoptosis, DNA-binding and antioxidant activity

Abstract

Two new ruthenium(II) polypyridyl complexes [Ru(dmb) 2(maip)](ClO 4) 2 1 (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline and [Ru(dmb) 2(maip)](ClO 4) 2 2 (paip = 2-(4-aminophenyl)imidazo[4,5-f][1,10]phenanthroline, dmb = 4,4′-dimethyl-2,2′-bipyridine) have been synthesized and characterized. The DNA-binding behaviors of complexes 1 and 2 were studied by viscosity measurements, thermal denaturation, photocleavage, absorption titration and luminescence spectra. The results show that the two complexes intercalate between the base pairs of DNA. The DNA-binding constants K b for complexes 1 and 2 were determined to be 1.12 ± 0.11 × 10 5 M −1 ( s = 2.17) and 3.46 ± 0.59 × 10 5 M −1 ( s = 2.11) M −1. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O 2 − ) and singlet oxygen ( 1O 2) may play an important role. The cytotoxicity of these complexes has been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The IC 50 values are 19.21, 33.15, 38.57 and 21.15 for complex 1 and 41.77, 123.58, 255.44 and 49.11 for complex 2 against BEL-7402, C-6, HepG-2 and MCF-7 cell lines, respectively. The apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining methods and the results indicate that complexes can induce the apoptosis of BEL-7402 cells. The experiments on antioxidant activity show these complexes exhibit good antioxidant activity against hydroxyl radical (OH ).