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

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...

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Main Authors: Simpson, Peter, Casari, Ilaria, Paternoster, Silvano, Skelton, B., Falasca, Marco, Massi, Massimiliano
Format: Journal Article
Published: Wiley - V C H Verlag GmbH & Co. KGaA 2017
Online Access:http://hdl.handle.net/20.500.11937/52825
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author Simpson, Peter
Casari, Ilaria
Paternoster, Silvano
Skelton, B.
Falasca, Marco
Massi, Massimiliano
author_facet Simpson, Peter
Casari, Ilaria
Paternoster, Silvano
Skelton, B.
Falasca, Marco
Massi, Massimiliano
author_sort Simpson, Peter
building Curtin Institutional Repository
collection Online Access
description 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.
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institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T09:53:15Z
publishDate 2017
publisher Wiley - V C H Verlag GmbH & Co. KGaA
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spelling curtin-20.500.11937-528252018-04-19T08:24:58Z 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 Casari, Ilaria Paternoster, Silvano Skelton, B. Falasca, Marco Massi, Massimiliano 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/52825 10.1002/chem.201701208 Wiley - V C H Verlag GmbH & Co. KGaA fulltext
spellingShingle Simpson, Peter
Casari, Ilaria
Paternoster, Silvano
Skelton, B.
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
title Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation
title_full Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation
title_fullStr Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation
title_full_unstemmed Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation
title_short Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation
title_sort defining the anti-cancer activity of tricarbonyl rhenium complexes: induction of g2/m cell cycle arrest and blockade of aurora-a kinase phosphorylation
url http://hdl.handle.net/20.500.11937/52825