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

Autor: Jakub Cervinka, Alberto Gobbo, Lorenzo Biancalana, Lenka Markova, Vojtech Novohradsky, Massimo Guelfi, Stefano Zacchini, Jana Kasparkova, Viktor Brabec, Fabio Marchetti
Přispěvatelé: Cervinka, Jakub, Gobbo, Alberto, Biancalana, Lorenzo, Markova, Lenka, Novohradsky, Vojtech, Guelfi, Massimo, Zacchini, Stefano, Kasparkova, Jana, Brabec, Viktor, Marchetti, Fabio
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Popis: 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.
Databáze: OpenAIRE