Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes

Abstract

The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5-(methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1 phase.

Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation

“…As the concentration of DNA increased, both absorption bands displayed clear hypochromism but no obvious red-shift. This observation is in agreement with recently published reports [63,64].…”

Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

“…All in all, the difference in cellular toxicity between [1](PF 6 ) 2 on the one hand, and [2](PF 6 ) 2 and [3](PF 6 ) 2 on the other hand, probably come from other reasons than differences in cellular uptake. Clear differences of localization and/or toxicity have been observed in other published series of ruthenium polypyridyl complexes containing one or several dipyridylamine ancillary ligands [51,52]. Probably, [Ru(tpy)(bpy)(OH 2 )] 2+ is simply less cytotoxic than its i-biq and i-Hdiqa analogs [4] 2+ and [5] 2+ , because of different cellular localization and/or interaction with biomolecules, which remains to be elucidated.…”

Advanced glycation end products, galectin-3, matrix metalloproteinase-9 activity in men with heart failure and concomitant benign prostatic hyperplasia with androgen deficiency

“…The zymograms were visualized and analyzed densitometrically.The results of the analysis were interpreted semi-quantitatively in arbitrary units (a.u.) of optic density compared to the control sample (men with HF without BPH) [11]. The level of galectin-3, CRP was determined by the method of immune-enzyme analysis with the commercial kit "AccuBind ELISA".…”