Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation

Peter V. Simpson, Ilaria Casari, Silvano Paternoster, Brian W. Skelton, Marco Falasca, Massimiliano Massi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Rhenium and ruthenium complexes containing N-heterocylic carbene (NHC) ligands and conjugated to indomethacin were prepared. The anticancer properties were probed against pancreatic cell lines, revealing a remarkable activity of the rhenium fragment as anticancer agent. The ruthenium complexes were found to be inactive against the same pancreatic cancer cell lines, either alone or in conjugation with indomethacin. An in-depth biological study revealed the origin of the anticancer properties of the rhenium tricarbonyl fragment, of which a complete elucidation had yet to be achieved. It was found that the rhenium complexes induce cell cycle arrest at the G2/M phase by inhibiting the phosphorylation of Aurora-A kinase. A preliminary study on the structure–activity relationship on a large family of these complexes revealed that the anticancer properties are mainly associated with the lability of the ancillary ligand, with inert complexes showing limited to no anticancer properties.

Original languageEnglish
Pages (from-to)6518-6521
Number of pages4
JournalChemistry - A European Journal
Volume23
Issue number27
DOIs
Publication statusPublished - 11 May 2017

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Aurora Kinase A
Rhenium
Phosphorylation
Cells
Ruthenium
Indomethacin
Ligands
Antineoplastic Agents

Cite this

Simpson, Peter V. ; Casari, Ilaria ; Paternoster, Silvano ; Skelton, Brian W. ; Falasca, Marco ; Massi, Massimiliano. / Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes : Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation. In: Chemistry - A European Journal. 2017 ; Vol. 23, No. 27. pp. 6518-6521.
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Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes : Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation. / Simpson, Peter V.; Casari, Ilaria; Paternoster, Silvano; Skelton, Brian W.; Falasca, Marco; Massi, Massimiliano.

In: Chemistry - A European Journal, Vol. 23, No. 27, 11.05.2017, p. 6518-6521.

Research output: Contribution to journalArticle

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