Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine–Thiosemicarbazone Hybrids

Organoruthenium complexes are potent
alternatives for platinum-based
complexes because of their superior anticancer activity. In this investigation,
a series of new Ru­(II)-arene complexes with triarylamine–thiosemicarbazone
hybrid ligands with higher anticancer activity than cisplatin are
reported. The molecular structure of the ligands and complexes was
confirmed spectroscopically and supported by single-crystal X-ray
crystallography. These complexes adopted a three-leg piano stool geometry.
All the Ru­(II)-arene complexes were systematically investigated for
their in vitro cytotoxicity against human cervical (HeLa S3), lung
(A549) cancer, and human normal lung (IMR-90) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay. Interestingly, a pyrrolidine-attached Ru­(II)-benzene
complex exhibited superior activity against cancer cells with low
IC50 values, and colony formation study showed complete
inhibition at 5 and 10 μM concentration. Furthermore, morphological
changes assessed by acridine orange and propidium iodide staining
revealed that the cell death occurred by apoptosis. In addition, the
interaction between synthesized Ru­(II)-arene complexes and DNA/protein
was explored by absorption and emission spectroscopy methods. These
synthesized new organoruthenium complexes can be used for developing
new metal-based anticancer drugs.