Ruthenium(II)‐Dithiocarbazates as Anticancer Agents: : Synthesis, Solution Behavior, and Mitochondria‐Targeted Apoptotic Cell Death

The reaction of the Ru(PPh 3 ) 3 Cl 2 with HL 1−3 −OH (−OH stands for the oxime hydroxyl group; HL 1 −OH=diacetylmonoxime‐S‐benzyldithiocarbazonate; HL 2 −OH=diacetylmonoxime‐S‐(4‐methyl)benzyldithiocarbazonate; and HL 3 −OH=diacetylmonoxime‐S‐(4‐chloro)benzyl‐dithiocarbazonate) gives three new ruthenium complexes [Ru II (L 1−3 −H)(PPh 3 ) 2 Cl] ( 1 – 3 ) (−H stands for imine hydrogen) coordinated with dithiocarbazate imine as the final products. All ruthenium(II) complexes ( 1 – 3 ) have been characterized by elemental (CHNS) analyses, IR, UV‐vis, NMR ( 1 H, 13 C, and 31 P) spectroscopy, HR‐ESI‐MS spectrometry and also, the structure of 1 – 2 was further confirmed by single crystal X‐ray crystallography. The solution/aqueous stability, hydrophobicity, DNA interactions, and cell viability studies of 1 – 3 against HeLa, HT‐29, and NIH‐3T3 cell lines were performed. Cell viability results suggested 3 being the most cytotoxic of the series with IC 50 6.9±0.2 μM against HeLa cells. Further, an apoptotic mechanism of cell death was confirmed by cell cycle analysis and Annexin V‐FITC/PI double staining techniques. In this regard, the live cell confocal microscopy results revealed that compounds primarily target the mitochondria against HeLa, and HT‐29 cell lines. Moreover, these ruthenium complexes elevate the ROS level by inducing mitochondria targeting apoptotic cell death.