Formation, biomolecular interaction and cytotoxicity studies of new organoruthenium Schiff base compounds

Abstract

Cytotoxic effects of arene ruthenium(II) compounds have been fine-tuned by the inherent lipophilic character of their arene moiety and the inclusion of different biomarkers within their coordination spheres. Herein, we demonstrate the formation and characterization of novel diamagnetic p-cymene ruthenium compounds: (µ-S)2[Ru(η6-p-cymene)(tmc)]2(PF6)2 (1) (Htmc = 1-((thiophen-2-yl)methylene)thiosemicarbazide), [Ru(η6-p-cymene)(ap)Cl](PF6) (2) (ap = 4-aminoantipyrene), [Ru(η6-p-cymene)(cinap)Cl](PF6) (3) (cinap = 1,5-dimethyl-2-phenyl-4-10-1,2-dihydro-3H-pyrazol-3-one), and [Ru(η6-p-cymene)(cumbh)Cl] (4) (cumbh = N-(4-isopropylbenzylidene)benzohydrazide)). The compounds were less toxic than the cisplatin and NAMI-A controls in all cell lines tested and, except for 3, were generally more cytotoxic to the breast cancer cells than the HeLa cells, displaying half maximal inhibitory concentration (IC50) values in the micromolar range. The effect of compounds 1–4 on long-term survival using a clonogenic assay was assessed in the TNBC HCC1806 cell, where all the compounds reduced colony formation thus adversely affected the long-term survival of the HCC1806 cells. Inhibitory effects of the compounds 1–4 on Topoisomerase I (Topo I) function were assessed. Biomolecular interaction investigations between human genomic DNA and the individual metal complexes indicated that they are likely groove-binders or partial intercalators with intrinsic binding constants in the order of 104 M−1.