Highly Cytotoxic Molybdenocenes with Strong Metabolic Effects Inhibit Tumour Growth in Mice

Chemistry. 2023 Jan 18;29(4):e202202648. doi: 10.1002/chem.202202648. Epub 2022 Nov 29.

Abstract

A series of six highly lipophilic Cp-substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X-ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non-Cp-substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph2 C-Cp)2 MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin-associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.

Keywords: anticancer; biological tests (in vitro and in vivo); bioorganometallic chemistry; molybdenocenes; proteomics.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Chelating Agents / chemistry
  • Crystallography, X-Ray
  • Ligands
  • Mice
  • Molecular Structure
  • Neoplasms*
  • Proteomics

Substances

  • Antineoplastic Agents
  • Chelating Agents
  • Ligands