A bis-indazolic ruthenium(II) complex: Reactivity and biological studies on cancer 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-[Ru-II(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 Bronsted-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 mu mol 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.