Antitumor activity of ruthenium(III) complexes with [N2O2]-tetradentate Schiff base ligands

Abstract

In this article, the antitumor and antiproliferative activity of three Ru(III) complexes, [Ru^III(Salen)(PPh₃)Cl] (RuSalen), [Ru^III(Salphen)(PPh₃)Cl] (RuSalphen), and [Ru^III(Salpn)(PPh₃)Cl] (RuSalpn) (H₂Salen, H₂Salphen and H₂Salpn are the Schiff bases obtained by the condensation between salicylaldehyde and ethylenediamine, 1,2-phenylenediamine, and 1,3-diaminopropanne, respectively) and their precursor, [Ru^II(PPh₃)₃Cl₂], were investigated against laboratory-cultured tumor cell lines: HT29 (human colorectal carcinoma), Saos-2 (human osteogenic sarcoma), HeLa (human cervical carcinoma), RST (rat transplantable sarcoma), and the non-tumor cell line Lep3 (embryonal human fibroblasts). It was found that all the cancer cell lines investigated were effectively dose-dependently inhibited in their growth by the Ru(III) complexes, while the non-tumor cell line Lep3 was the least affected by their cytotoxic effect. The Annexin V assay revealed that the Ru(III) complexes determined the occurrence of apoptosis in all cell lines tested, in a dose-dependent manner. RuSalpn exhibited the strongest ability to reduce tumor cell survival and proliferation, with efficacy that is either superior to or comparable to that of well-established clinical oncology agents such as cisplatin, oxaliplatin, epirubicin, and paclitaxel. The experiments revealed a cell-specific response, with varying degrees of sensitivity to the tested substances across different cell lines. RuSalpn demonstrated the strongest cytotoxic effect in the HT29 cell line, while RuSalen, RuSalphen showed the highest activity against RST cells. It was found that RuSalphen (≥7.0 μM) significantly inhibited cell migratory activity in the HT29 cell line, while in the RST cell line, RuSalen (≥37.6 μM), RuSalphen (≥14.0 μM), and RuSalpn (≥36.8 μM) demonstrated a strong inhibitory effect on cell migration.