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Home / Equine Research Bank / J Biol Inorg Chem / Ruthenium anticancer drugs and proteins: a study of the inte...
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2007; 12(8); 1107-1117; doi: 10.1007/s00775-007-0280-4

Ruthenium anticancer drugs and proteins: a study of the interactions of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)] with hen egg white lysozyme and horse heart cytochrome c.

Abstract: The interactions with protein targets of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)], NAMI-A, an effective anticancer and antimetastatic agent now in clinical trials, deserve great attention as they are believed to be at the basis of the mechanism of action of this innovative molecule. Here, we report on the reactions of NAMI-A with two well-known model proteins, namely, hen egg white lysozyme and horse heart cytochrome c; these reactions were investigated by a variety of physicochemical methods, including optical spectroscopy, (1)H NMR and electrospray ionization mass spectrometry. The combined use of the analytical techniques mentioned resulted in a rather exhaustive description of the NAMI-A-protein interactions; in particular, the formation of fairly stable metal-protein adducts was clearly documented and the nature of the resulting protein-bound metallic fragments ascertained in most cases. Notably, greatly different patterns of interaction were found to be operative for NAMI-A toward these two proteins. The biological implications of the present findings are discussed.
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Publication Date: 2007-08-07 PubMed ID: 17680283DOI: 10.1007/s00775-007-0280-4Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examines how a promising anticancer and antimetastatic drug, known as NAMI-A, interacts with two model proteins. Using different techniques, the study illuminates the formation and nature of the metal-protein adducts, giving crucial insight into how NAMI-A might function biologically against cancer.

NAMI-A and Protein Interaction

  • The study investigates a ruthenium(III) complex called NAMI-A, which is currently in clinical trials for its anticancer and antimetastatic properties.
  • The focus is on the mechanisms of interaction between NAMI-A and proteins, believed to be the foundation behind the drug’s function.
  • Two proteins are targets of this exploration: hen egg white lysozyme and horse heart cytochrome c, both commonly employed as model proteins in biomedical research.

Methodological Procedure

  • The research harnesses various physicochemical methods, including optical spectroscopy, proton nuclear magnetic resonance ((1)H NMR), and electrospray ionization mass spectrometry.
  • These methods generate a comprehensive understanding of the interactions between NAMI-A and the chosen proteins.
  • A key achievement is the successful characterization of the metal-protein adducts – molecules formed by the reaction between the drug and the proteins. This allows a glimpse into the nature of the metallic fragments bound to the proteins after interaction.

Assessment and Biologically Relevant Outcomes

  • The metal-protein adducts formed by NAMI-A and the proteins displayed appreciable stability, attesting to the strong interaction between the drug and the model proteins.
  • Strikingly, NAMI-A exhibits differing manners of interaction with each protein, suggesting it has variable ways of binding to different molecular targets.
  • The findings form crucial pieces of a puzzle – the therapeutic mechanism of a potential anticancer drug. This sets the stage for further inquiries into the precise ways in which NAMI-A operates against cancer cells.

Cite This Article

APA
Casini A, Mastrobuoni G, Terenghi M, Gabbiani C, Monzani E, Moneti G, Casella L, Messori L. (2007). Ruthenium anticancer drugs and proteins: a study of the interactions of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)] with hen egg white lysozyme and horse heart cytochrome c. J Biol Inorg Chem, 12(8), 1107-1117. https://doi.org/10.1007/s00775-007-0280-4

Publication

Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
ISSN: 0949-8257
NlmUniqueID: 9616326
Country: Germany
Language: English
Volume: 12
Issue: 8
Pages: 1107-1117

Researcher Affiliations

Casini, Angela
  • Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, Italy.
Mastrobuoni, Guido
    Terenghi, Mattia
      Gabbiani, Chiara
        Monzani, Enrico
          Moneti, Gloriano
            Casella, Luigi
              Messori, Luigi

                MeSH Terms

                • Animals
                • Antineoplastic Agents / chemistry
                • Cytochromes c / chemistry
                • Dimethyl Sulfoxide / analogs & derivatives
                • Dimethyl Sulfoxide / chemistry
                • Horses
                • Magnetic Resonance Spectroscopy
                • Muramidase / chemistry
                • Organometallic Compounds / chemistry
                • Ruthenium / chemistry
                • Ruthenium Compounds
                • Spectrometry, Mass, Electrospray Ionization

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