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

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, (Ph2C-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.

Automated summary

A series of highly lipophilic Cp-substituted molybdenocenes with different bioactive chelating ligands were synthesized and characterized. They showed significantly increased cytotoxic potency compared to non-Cp-substituted counterparts. In vivo experiments demonstrated tumor growth inhibition for the most active complex containing the thioflavone ligand, along with significant regulation of tubulin-associated and mitochondrial inner membrane proteins.