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

Two new ruthenium(II) polypyridyl complexes [Ru(dmb)(2)(maip)](ClO4)(2) 1 (maip = 2-(3-aminophenyl)imizado[4,5-f][1,10]phenanthroline and [Ru(dmb)(2)(maip)](ClO4)(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 I 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 x 10(5) M-1 (s = 2.17) and 3.46 +/- 0.59 x 10(5) M-1 (s = 2.11) M-1. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O-2(center dot-)) and singlet oxygen (O-1(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 IC50 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 center dot). Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.