New Organometallic Ru(II) Compounds with Lonidamine Motif as Antitumor Agents

The combination of one molecule of organic and metal-based fragments that exhibit antitumor activity is a modern approach in the search for new promising drugs. In this work, biologically active ligands based on lonidamine (a selective inhibitor of aerobic glycolysis used in clinical practice) were introduced into the structure of an antitumor organometallic ruthenium scaffold. Resistant to ligand exchange reactions, compounds were prepared by replacing labile ligands with stable ones. Moreover, cationic complexes containing two lonidamine-based ligands were obtained. Antiproliferative activity was studied in vitro by MTT assays. It was shown that the increase in the stability in ligand exchange reactions does not influence cytotoxicity. At the same time, the introduction of the second lonidamine fragment approximately doubles the cytotoxicity of studied complexes. The ability to induce apoptosis and caspase activation in tumour cell MCF7 was studied by employing flow cytometry.

Automated summary

The combination of organic and metal-based fragments with antitumor activity is a modern approach to discover new drugs. This study introduces biologically active ligands based on lonidamine into antitumor organometallic ruthenium scaffold. The stability in ligand exchange reactions does not affect cytotoxicity, while the introduction of a second lonidamine fragment doubles the cytotoxicity. The ability to induce apoptosis and caspase activation in tumor cells was also studied.