Belgrade : Serbian Association for Cancer Research
Abstract
Background: Ruthenium containing compounds represent the most promising alternative to platinum-based chemotherapeutics whose therapeutic value has been limited by significant side effects. Advantageous features such as good aqueous solubility and relatively inert arene ligand make them very attractive for structural optimizations aimed for improved in vivo potency. Material and Methods: Reported complexes were obtained in a reaction of [Ru(η6-benzene)Cl(μ-Cl)]2 or [Ru(η6-toluene)Cl(μ-Cl)]2 with picolinic acid or 6-fluoropicolinic acid in a 1:2 molar ratio in ethanol and characterized by IR and NMR spectroscopy and MS spectrometry. Results: The cytotoxic profile was investigated by the colorimetric MTT assay, in a panel of human non-malignant cell line (MRC-5), and cancer cell lines (A549, HTB177, PC3, A375, HeLa, HCT116, MDA-MB-453). The complexes carrying picolinic acid, displayed moderate antiproliferative effect particularly toward colorectal carcinoma (HCT116) and cervix adenocarcinoma cells (HeLa). The highest activity and cytoselectivity was observed for complex with [Ru(η6-benzene)Cl(μ-Cl)]2 toward HCT116 cells: it was capable of reducing viability of HCT116 cells 1.5 times more efficiently (IC50 = 27.5 μM), than of the MRC-5 cells (IC50 = 41.3 μM). Conclusion: The complex with improved activity and selectivity is candidate for further investigations regarding its binding modes, sites, and affinities
