Development of 2‐Bis(Quinolin‐2‐Ylmethylene)Hydrazine‐Based Half‐Sandwich Ruthenium(II) Arene Complexes with High Cytotoxicity in Castration‐Resistant Prostate Cancer Cells

Metal complexes that can target uncurable forms of cancer are in high demand. Presented herein is detailed characterization, anticancer activity and structure–activity comparison for a set of Ru(II) arene chlorido organometallic complexes [(η 6 ‐arene)(L)RuCl]PF 6 ( BzRuL and HmbRuL ) using 2‐bis(quinolin‐2‐ylmethylene) hydrazine ( L ) as ligand. BzRuL and HmbRuL was characterized by elemental analyses, FTIR, 1 H, 13 C‐NMR, 1 H– 1 H COSY‐NMR, and ESI mass spectroscopy. Spectroscopic and single‐crystal X‐ray diffraction (XRD) analysis suggested that the complexes BzRuL and HmbRuL exhibit a piano‐stool structure. These complexes exhibit potent anticancer activity (IC 50 9.62 μM for BzRuL and 7.23 μM for HmbRuL ) even more effective than the standard drug cisplatin in a castration‐resistant human prostatic adenocarcinoma cell line (PC‐3). Their comparative analysis with our recently reported highly active Ru(II) complex with same ligand pCYRuL (IC 50 0.71 μM) is also presented. Both the complexes interact with dsDNA and likely induce apoptosis via DNA damage pathway. This study introduces a new family of Ru complexes with promising potential for preclinical development against incurable prostate cancer.