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|Title:||Tetranuclear Polypyridylruthenium(II) complexes as inhibitors and down-regulators of Phosphatase enzymes|
|Citation:||ChemistrySelect, 2017; 2(33):10688-10672|
|Madhu K. Sundaraneedi, Alaina J. Ammit, Bemnet A. Tedla, Mark S. Pearson, Alex Loukas, F. Richard Keene, and J. Grant Collins|
|Abstract:||Mitogen-activated protein kinase phosphatases (MKPs) are over-expressed in many cancers. The increased levels of MKP enzymes protect cells from apoptosis induced by anticancer drugs, and thereby decrease the efficacy of the drug. Consequently, there is considerable interest in the development of agents that can down-regulate the production of the MKP enzymes or inhibit their catalytic activities. We have examined the ability of a series of oligonuclear polypyridylruthenium(II) complexes to inhibit the activity of MKP-1 and MKP-3. The results demonstrated that two tetranuclear complexes inhibit the activity of MKP-1 and MKP-3 at 10-20 μM concentrations. The ability of the ruthenium complexes to inhibit the production of MKP-1 in live cancer cells was demonstrated through Western blotting assays, while real-time reverse transcription polymerase chain reaction assays demonstrated the tetranuclear complexes decreased the amount of mkp-1 mRNA produced in cancer cells. The results of this study suggest that tetranuclear ruthenium complexes could be used to enhance the antiproliferative effect of anticancer drugs.|
|Rights:||©2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim|
|Appears in Collections:||Chemistry and Physics publications|
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