Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for in vitro anti-tumour activity in human glioblastoma cancer cell lines and in vivo toxicity studies in a zebrafish model.

Abstract

Herein, we have introduced a series of half-sandwich Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for brain cancer therapy. Among all the synthesized complexes, [(η6-p-cymene)RuII(κ2-N,N-4,7dimethyl phenanthroline)(PTA)]·2PF6 (4c) and [(η6-p-cymene)RuII(κ2-N,N-4,7diphenyl phenanthroline)(PTA)]·2PF6 (4d) showed outstanding potency against the T98G, LN229 and U87MG cancer cells. The antiproliferative activity of these complexes was reinforced by neurosphere, DNA intercalation, agarose gel electrophoresis, cell cycle analysis and time-dependent ROS detection assays. The real-time reverse transcription (RT)-polymerase chain reaction (PCR) study showed that complex 4c inhibited the TNF-α-induced NF-κB phosphorylation in glioma cells. Moreover, the in vivo biodistribution of complex 4c in different organs and the morphological patterns of widely used zebrafish embryos due to toxic effects have been evaluated.