Copper complexes against multi-drug resistant solid tumours

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Platinum-based drugs are still one of the golden standards for treating many tumours. However, the search for safer and more effective anticancer drugs never stops. In this regard, copper-based complexes have recently received considerable attention thanks to their in vitro and in vivo properties, which include improved selectivity toward tumour cells, reduced side effects, and efficacy against tumours resistant to platinum-based drugs.

Professors Valentina Gandin (University of Padova), Maura Pellei, Wilma Quaglia (University of Camerino), and collaborators, realised and tested several metal complexes based on copper and lonidamide (LND), an antitumour drug capable of sensitising tumours to radio-, chemo-, and photodynamic therapy. The complexes’ molecular structure and stability were confirmed by Synchrotron Radiation-based X-ray Photoelectron Spectroscopy (SR-XPS) performed by Professor Chiara Battocchio (University Roma Tre) at the Materials Science Beamline (MSB), available at the Czech CERIC Partner Facility at the Elettra Synchrotron in Trieste. The different molecules were also tested against various tumour cells, including multi-drug-resistant cancer cell lines.

The antineoplastic drug lonidamine was conjugated with bis(pyrazolyl)acetates to obtain new Cu(I) and Cu(II) complexes, whose electronic and molecular structures were investigated by SR-XPS and XAS. All complexes showed significant anticancer activity in human tumour cell lines and were more effective than cisplatin against 3D spheroids of PSN-1 cancer cells. Moreover, although to a different extent, the most interesting complexes proved to accumulate into cancer cells.

The synergistic mechanisms of action due to the presence of LND and copper in the same molecule led to an exceptionally promising activity against tumour cells, even against oxaliplatin and multi-drug resistant cell lines. Such results show that copper-LND conjugated complexes are a valid alternative for treating solid tumours refractory to platinum-based treatments and deserve further investigation.

ORIGINAL ARTICLE:

CU (I) AND CU (II) COMPLEXES BASED ON LONIDAMINE-CONJUGATED LIGANDS DESIGNED TO PROMOTE SYNERGISTIC ANTITUMOR EFFECTS. DEL BELLO F., PELLEI M., BAGNARELLI L., SANTINI C., GIORGIONI G., PIERGENTILI A., QUAGLIA W., BATTOCCHIO C., IUCCI G., SCHIESARO I., MENEGHINI C., VENDITTI I., RAMANAN N., DE FRANCO F., SGARBOSSA P., MARZANO C., & GANDIN V., INORGANIC CHEMISTRY, 2022.