Improved Synthesis, Anticancer Activity and Electrochemical Characterization of Unusual Zwitterionic Palladium Compounds with a Ten‐Term Coordinative Ring.

Abstract

A new improved synthetic protocol for the preparation of uncommon zwitterionic palladium(II) complexes with a tenterm coordinative ring is reported. A suitable combination of reaction solvent and temperature allows to drastically reduce the reaction time and increase the yield. A detailed kinetic study, implemented by theoretical DFT calculations, clarifies and quantifies this solvent effect. The antiproliferative activity of the synthesized complexes was tested toward eight different cancer cell lines. The mesityl derivative showed potent and selective cytotoxicity toward several types of cancer cell lines, with IC 50 values lower than cisplatin. Additionaly, the anticancer activity against cisplatin-sensitive and cisplatin-resistant ovarian cancer cells suggested a different mechanism of action with respect to traditional platinum chemotherapeutics. Aiming to easily determine these promising metallo-drugs, a voltammetric study of their electrochemical fingerprint was carried out. For both compounds a suitable signal, ascribed to the reduction of the metallic center from palladium(II) to palladium (0), was identified and further investigated by Differential Pulse Voltammetry.

Rational Design of Palladium(II) Indenyl and Allyl Complexes Bearing Phosphine and Isocyanide Ancillary Ligands with Promising Antitumor Activity

“…Therefore, medical researchers are particularly interested in identifying new therapeutic approaches to overcome this issue. In some of our previous works, we proved that palladium-based drugs can represent a potential interesting option for treating this type of disease [ 31 , 32 , 56 , 57 ]; therefore, we planned to test the new complexes prepared in this work to assess their cytotoxicity towards ovarian cancer cells. Moreover, we also decided to explore the anticancer activity of these compounds against one of the most aggressive breast cancer cell lines, known as MDA-MB-231 (triple-negative breast cancer).…”

Bilateral metalloheterocyclic systems based on palladacycle and piperidine-2,4-dione pharmacophores

“…1). [31][32][33][34][35][36][37][38] In many cases palladacycles have demonstrated an activity that is several orders higher relative to Pt-complexes, while maintaining a less cytotoxic effect on healthy cells. Nevertheless, to date, no palladium complex has been approved for use as an anticancer drug.…”

Reactions of proteins with a few organopalladium compounds of medicinal interest

“… 1 Indeed, a number of palladium complexes with innovative features and encouraging anticancer properties were recently prepared, characterized and tested by Visentin and co-workers. 2 In particular, the most interesting compounds contain the palladium-η 3 -allyl and palladacyclopentadienyl fragments.…”