New dinuclear arene Ru(ii) benzilbis(furoylhydrazone) complexes: synthesis, structure, and anticancer activity

Abstract

We report the synthesis of new set of organometallic dinuclear ruthenium(II) arene complexes along with studies on their in vitro antiproliferative activity and cancer cell death mechanism. Specifically, dinuclear ruthenium complexes of the type [(η⁶-p-cymene)₂Ru₂(L)Cl₂] (1–3) (L = benzil bis(furoylhydrazone derivatives)) were synthesized. The formation of the complexes was well examined by elemental analysis and spectroscopic studies, including FT-IR, UV-vis, NMR, and HR-MS. The existence of a piano-stool structure was evinced by single-crystal X-ray crystallographic technique and confirmed the coordination of furoylhydrazone to each ruthenium metal centre via a hydrazone nitrogen and imidolate oxygen. Further, the cancerous cell growth resistance property of all the complexes against human cancer cell lines, such as A549 (lung carcinoma) and HeLa (cervical cancer), was assessed by MTT assay along with the standard drug cisplatin. It was noted that complex 2 exhibited a two-fold higher activity in inhibition of all the cancer cells than cisplatin. This may be attributed to the existence of an electron-releasing methyl substituent of the ligand, which subsequently increased hydrophobicity. Further, fluorescent staining methods, including dual AO-EB and DAPI, confirmed apoptosis occurred through morphological changes. In addition, quantitative discrimination of late apoptosis by the externalization of phosphatidylserine was confirmed by flow cytometry using annexin V-FITC/propidium iodide (PI) double-staining.