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

[Image: see text] 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 proc...

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Autores principales: Cervinka, Jakub, Gobbo, Alberto, Biancalana, Lorenzo, Markova, Lenka, Novohradsky, Vojtech, Guelfi, Massimo, Zacchini, Stefano, Kasparkova, Jana, Brabec, Viktor, Marchetti, Fabio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376960/
https://www.ncbi.nlm.nih.gov/pubmed/35913426
http://dx.doi.org/10.1021/acs.jmedchem.2c00722
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author Cervinka, Jakub
Gobbo, Alberto
Biancalana, Lorenzo
Markova, Lenka
Novohradsky, Vojtech
Guelfi, Massimo
Zacchini, Stefano
Kasparkova, Jana
Brabec, Viktor
Marchetti, Fabio
author_facet Cervinka, Jakub
Gobbo, Alberto
Biancalana, Lorenzo
Markova, Lenka
Novohradsky, Vojtech
Guelfi, Massimo
Zacchini, Stefano
Kasparkova, Jana
Brabec, Viktor
Marchetti, Fabio
author_sort Cervinka, Jakub
collection PubMed
description [Image: see text] 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.
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spelling pubmed-93769602022-08-16 Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis Cervinka, Jakub Gobbo, Alberto Biancalana, Lorenzo Markova, Lenka Novohradsky, Vojtech Guelfi, Massimo Zacchini, Stefano Kasparkova, Jana Brabec, Viktor Marchetti, Fabio J Med Chem [Image: see text] 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. American Chemical Society 2022-08-01 2022-08-11 /pmc/articles/PMC9376960/ /pubmed/35913426 http://dx.doi.org/10.1021/acs.jmedchem.2c00722 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Cervinka, Jakub
Gobbo, Alberto
Biancalana, Lorenzo
Markova, Lenka
Novohradsky, Vojtech
Guelfi, Massimo
Zacchini, Stefano
Kasparkova, Jana
Brabec, Viktor
Marchetti, Fabio
Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title_full Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title_fullStr Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title_full_unstemmed Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title_short Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis
title_sort ruthenium(ii)–tris-pyrazolylmethane complexes inhibit cancer cell growth by disrupting mitochondrial calcium homeostasis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376960/
https://www.ncbi.nlm.nih.gov/pubmed/35913426
http://dx.doi.org/10.1021/acs.jmedchem.2c00722
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