Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis

While ruthenium arene complexes have been widely investigated
for
their medicinal potential, studies on homologous compounds containing
a tridentate tris­(1-pyrazolyl)­methane ligand are almost absent in
the literature. Ruthenium­(II) complex 1 was obtained
by a modified reported procedure; then, the reactions with a series
of organic molecules (L) in boiling alcohol afforded novel complexes 2–9 in 77–99% yields. Products 2–9 were fully structurally characterized. They are
appreciably soluble in water, where they undergo partial chloride/water
exchange. The antiproliferative activity was determined using a panel
of human cancer cell lines and a noncancerous one, evidencing promising
potency of 1, 7, and 8 and
significant selectivity toward cancer cells. The tested compounds
effectively accumulate in cancer cells, and mitochondria represent
a significant target of biological action. Most notably, data provide
convincing evidence that the mechanism of biological action is mediated
by the inhibiting of mitochondrial calcium intake.