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

J. Cervinka, A. Gobbo, L. Biancalana, L. Markova, V. Novohradsky, M. Guelfi, S. Zacchini, J. Kasparkova, V. Brabec, F. Marchetti

. 2022 ; 65 (15) : 10567-10587. [pub] 20220801

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024851

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.

Citace poskytuje Crossref.org

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