Ruthenium(II)–tris-pyrazolylmethane complexes inhibit cancer cell growth by disrupting mitochondrial calcium homeostasis

Journal: Journal of Medicinal Chemistry
Authors: Cervinka J., Gobbo A., Biancalana L., Markova L., Novohradsky V., Guelfi M., Zacchini S., Kasparkova J., Brabec V., Marchetti F.
Year: 2022
ISBN: 0022-2623

Abstract

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.