Platinum(ii/iv) complexes with N-substituted carboxylate ethylenediamine/propylenediamine ligands: preparation, characterization and in vitro activity

Abstract

The synthesis and characterization of novel platinum(II) and platinum(IV) complexes derived from unsymmetrical ethylene or propylenediamine derivatives are presented. IR spectroscopy and ESI mass spectrometry techniques were employed to characterize the complexes, revealing distinctive absorption bands and isotope patterns. Furthermore, the complexes were characterized by ¹H and ¹³C NMR spectroscopy. Single-crystal X-ray structural analysis elucidated the coordination geometry and intermolecular interactions of complexes 3, 4 and 6. Cytotoxicity evaluation of the complexes on various cell lines highlighted complex 3 as the most active, realizing its tumoricidal activity through induction of apoptosis and increased total caspase activity in MCF-7 cells. Since its application is followed by cytoprotective autophagy, the effectiveness can be additionally empowered by concomitant inhibition of this process. Furthermore, the Pt^IV compound 3 induces oxidative stress in hemoglobin, and is reducible by glutathione, suggesting its potential as a carrier for the active Pt^II precursor 2a to cancer cells without increasing cytotoxicity. Cyclic voltammetry corroborates the ability of complex 3 to undergo reduction under physiological conditions.