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Versatile analytical methodology for evaluation of drug-like properties of potentially multi-targeting anticancer metallodrugs

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Abstract

Using inductively coupled plasma mass spectrometry (in combination with ultrafiltration) and microemulsion electrokinetic chromatography, the drug properties of two new, potentially multi-targeting Ru(III) and Pt(IV) compounds, containing biologically active ligands, were evaluated. The ruthenium complex with bexarotene was shown to bind to albumin faster than to transferrin and exhibits much the same (to albumin) binding profile in human serum. The Pt(IV)–lonidamine complex interacts with albumin relatively slowly but possesses high stability and lipophilicity (log P 1.62), which makes it possible the cellular uptake in a free (of proteins) form. Although both examined compounds display a moderate solubility (below 10–4 M), this stands compatible with their nanomolar cytotoxic activities. The Ru(III) compound, whose active moiety is a complexed anion, is deemed promising to be loaded on nanoscale anion-exchangers with the aim of controlled delivery.

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Acknowledgements

This work was supported by the Project of the State Assignment (Vernadsky Institute of Geochemistry and Analytical Chemistry). The authors acknowledge with gratitude Dr. V. K. Karandashev for supervising ICP-MS measurements, I. V. Zenin for assistance with MEEKC experiments, and Dr. O. V. Kuznetsova for performing the artwork.

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Authors and Affiliations

  1. Vernadsky Institute of Geochemistry and Analytical Chemistry of Russian Academy of Sciences, Kosygin Str. 19, 119991, Moscow, Russian Federation

    Lidia S. Foteeva & Andrei R. Timerbaev

  2. Department of Medicinal Chemistry and Fine Organic Synthesis, Lomonosov Moscow State University, Leninskie Gory 1/3, 119991, Moscow, Russian Federation

    Yulia N. Nosova & Alexey A. Nazarov

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

    Bernhard K. Keppler

Authors
  1. Lidia S. Foteeva
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  2. Yulia N. Nosova
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  3. Alexey A. Nazarov
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  4. Bernhard K. Keppler
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  5. Andrei R. Timerbaev
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Correspondence to Andrei R. Timerbaev.

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Foteeva, L.S., Nosova, Y.N., Nazarov, A.A. et al. Versatile analytical methodology for evaluation of drug-like properties of potentially multi-targeting anticancer metallodrugs. ANAL. SCI. 38, 627–632 (2022). https://doi.org/10.1007/s44211-022-00076-9

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  • DOI: https://doi.org/10.1007/s44211-022-00076-9

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