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

Abstract

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 [(η⁶-arene)(L)RuCl]PF₆ (BzRuL and HmbRuL) using 2-bis(quinolin-2-ylmethylene) hydrazine (L) as ligand. BzRuL and HmbRuL was characterized by elemental analyses, FTIR, ¹H, ¹³C-NMR, ¹H–¹H 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 (IC₅₀ 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 (IC₅₀ 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.