A bis-indazolic ruthenium(II) complex: Reactivity and biological studies on cancer cells

A new KP1339 analogue ruthenium complex, cis-[Ru(Hind)2(bpy)2](PF6)2, showed expressive cytotoxicity against liver cancer cells, HepG2, causing DNA fragmentation, interrupting the cell cycle in phase S and resulting in cell death by apoptosis. [Display omitted] •Metal complexes exhibited anticancer activity against different tumor cell lines.•Suitable induction and selective cytotoxicity to cancer cell lines.•DNA fragmentation is a biological effect of the metal complex in HepG2 cells.•Cell death promoted by the bis-indazolic metal complex caused by apoptosis in HepG2 cells. Ru(II)-based complexes have been widely investigated as potential anticancer agents, leading cell death of tumor mass. In this work, a metal complex, cis-[RuII(Hind)2(bpy)2](PF6)2 (Hind = indazole and bpy = 2,2′-bipyridine), was synthesized and characterized by elemental analysis, spectroscopy and electrochemistry methods, validating its formulation. This complex can act as a Brønsted-Lowry acid with pKa close to physiological pH. Photosubstitution reaction was noticed upon blue light irradiation with release of indazol molecules in acetonitrile, a behavior also noticed, indicating its photosensitivity. This metal complex was screened in vitro against distinct human cancer cell lines. Hepatocellular carcinoma cells (HepG2) were the most sensitive, with the half maximal inhibitory concentration (IC50) at 7.2 µmol L−1. Further biological studies showed DNA fragmentation induced by this compound, which resulted in cell cycle arrest in S phase and HepG2 cell death by apoptosis. Moreover, there was no significant cytotoxicity against healthy human pulmonary fibroblast cells (MRC-5), and therefore the compound exhibited a high selectivity index, indeed a better in vitro anticancer profile than some structurally related compounds (e.g. NAMI-A and KP1039). Our results indicate exciting potential pharmacological applications of this metal complex in liver cancer treatment, which might be supported by further studies.