Synthesis and characterization of ruthenium(III) complex containing 2-aminomethyl benzimidazole, and its anticancer activity in in vitro and in vivo models

A novel ruthenium(III) complex with 2-aminomethyl benzimidazole (AMBI) has been synthesized and characterized by elemental analysis, spectroscopic (FTIR, UV–Vis and XRD), thermal, magnetic and electrochemical techniques. Characterization shown that the ruthenium ion is octahedral coordinated by three H2O molecules, one chloride ion and a bidentate AMBI. The calf thymus DNA binding activity of complex was studied by absorption spectra and viscosity measurements. The strong interaction between Ru(III) complex and CT-DNA was investigated and the Kb value equals 8.3 × 10⁻⁵. The cytotoxicity effect of water soluble [RuCl(AMBI)(H2O)3]Cl2 complex on breast adenocarcinoma (MCF-7) and human colon carcinoma (HCT-116) cell lines (in vitro) was investigated by the MTT method. The Ru(III) complex shows good cytotoxic activity and the IC50 values are 57.20 and 18.08 μg/mL toward MCF-7 and HCT-116, respectively. The antiproliferative effect of Ru(III) complex on HCT- 116 cells was nearly as the cisplatin value; that indicates its efficiency as anticancer agents. Apoptosis was studied by AO/EB staining and the Ru(III) complex shows apoptotic effect against the two cancer cell lines by percentage to 23.1 and 33.1%. DNA damage assay by gel electrophoresis was done and the DNA fragmentation that appears in the two treated lanes indicates that there was destruction in the nuclear DNA. The cell cycle arrest by flow cytometry showed that the Ru(III) complex stops the two cancer cell lines proliferation by decreasing the S and G0/G1 phases and increase in G2/M indicates that the interactions of our complex with DNA prevents the entry of cells into the DNA synthesis phase as well as into a new cell cycle. Moreover, the Ru(III) complex stops the proliferation of Ehrlich ascites carcinoma (EAC) bearing female mice (in vivo study) with low toxicity to the kidney. In addition, the antioxidant enzymes' activity in the treated and untreated groups' blood samples were also investigated. The decrease in topoisomerase I (Top I) levels in treated mice groups than the EAC group indicates the effect of our compound as topoisomerase I inhibitor.