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Understanding the interactions of diruthenium anticancer agents with amino acids

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Abstract

The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-κO)-2-methyl-4-(1H)-pyridinonato-κO4](η6-p-cymene)-ruthenium(II)}alkane (PyRu n2 ) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein–DNA and DNA–DNA crosslinking ability. We report here studies on the reactions of the diruthenium organometallics PyRu 62 and PyRu 82 in comparison with a mononuclear analogue PyRu3 with amino acids using mass spectrometry and NMR spectroscopy. The compounds behave very similarly, independent of the spacer length between the metal center and of the nuclearity of the complexes. Incubation with l-cysteine (Cys) results in fast release of the pyridone ligand, with the Ru complexes able to form Cys adducts. In contrast, l-methionine forms, initially, adducts with the metal centers, but over time, the adducts decompose. Similar behavior was observed for the reaction with l-histidine with [Ru(η6-p-cymene)(l-histidine)] species detected.

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Acknowledgements

We thank the organizations and foundations that have supported our research efforts in this area, especially the Universities of Auckland and Vienna, EPFL, and A.A.N. is grateful to the RFBR (16-03-00743).

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Authors and Affiliations

  1. M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, 119991, Moscow, Russia

    Alexey A. Nazarov

  2. Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria

    Maria-Grazia Mendoza-Ferri & Bernhard K. Keppler

  3. School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Muhammad Hanif & Christian G. Hartinger

  4. Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), 1015, Lausanne, Switzerland

    Paul J. Dyson

Authors
  1. Alexey A. Nazarov
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  2. Maria-Grazia Mendoza-Ferri
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  3. Muhammad Hanif
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  4. Bernhard K. Keppler
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  5. Paul J. Dyson
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  6. Christian G. Hartinger
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Corresponding authors

Correspondence to Alexey A. Nazarov or Christian G. Hartinger.

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Nazarov, A.A., Mendoza-Ferri, MG., Hanif, M. et al. Understanding the interactions of diruthenium anticancer agents with amino acids. J Biol Inorg Chem 23, 1159–1164 (2018). https://doi.org/10.1007/s00775-018-1597-x

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  • DOI: https://doi.org/10.1007/s00775-018-1597-x

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