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

Anal Sci. 2022 Mar;38(3):627-632. doi: 10.1007/s44211-022-00076-9. Epub 2022 Feb 21.

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.

Keywords: Anticancer metal-based drugs; ICP-MS; Lipophilicity; Microemulsion electrokinetic chromatography; Solubility; Transport plasma proteins.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Humans
  • Ligands
  • Organometallic Compounds* / chemistry
  • Pharmaceutical Preparations
  • Ruthenium* / chemistry
  • Transferrin / chemistry
  • Transferrin / metabolism

Substances

  • Antineoplastic Agents
  • Ligands
  • Organometallic Compounds
  • Pharmaceutical Preparations
  • Transferrin
  • Ruthenium