Tetranuclear polypyridylruthenium(II) complexes as inhibitors and down-regulators of phosphatase enzymes

Sundaraneedi, Madhu K., Ammit, Alaina, Tedla, Bemnet A., Pearson, Mark S., Loukas, Alex, Keene, F. Richard, and Collins, J. Grant (2017) Tetranuclear polypyridylruthenium(II) complexes as inhibitors and down-regulators of phosphatase enzymes. ChemistrySelect, 2 (33). pp. 10668-10672.

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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 mM 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 tetra nuclear complexes decreased the amount of mop-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.

Item ID: 52659
Item Type: Article (Research - C1)
ISSN: 2365-6549
Keywords: enzyme down-regulation; enzyme inhibition; MKP-1 and MKP-3; phosphatase enzymes; ruthenium complexes
Funders: University of New South Wales, Canberra, National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC Program Grant 1037304, NHMRC Senior Research Fellowship 1117504
Date Deposited: 26 Feb 2018 00:20
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 30%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060107 Enzymes @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 30%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 30%
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