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

New organoruthenium(II) Schiff base compounds were synthesized and characterized. These metal compounds illustrated optimal affinities towards Bovine Serum Albumin and Deoxyribonucleic acid as well as could inhibit Topoisomerase I function. Anticancer studies revealed that, in general, the compounds display selectivity for breast cancer cells compared to cervical cancer cells. [Display omitted] •Formation and characterization of novel diamagnetic para-cymene ruthenium compounds.•Effects of metal compounds on in vitro long-term survival using a clonogenic assay.•Cytotoxic effects of the arene ruthenium(II) compounds were investigated.•Inhibitory effects of the metal compounds on Topoisomerase I function were assessed.•Biomolecular interaction capabilities of the metal compounds were explored. 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.