Two bis-maltol-polyamines: Synthesis, characterization and studies of their palladium(II) complexes exploring their potential anticancer activity

The interest in the antineoplastic and binding properties shown by the bis-maltol polyamine family, particularly Malten and Maltonis, prompted us to study the Pd²⁺ complexes of these latter from both a biological and metallo-receptor point of view. The Malten-Pd²⁺ complex can lodge hard species such as Sr²⁺ in its coordination-driven preorganized pocket, as confirmed by X-ray diffraction. UV-Vis and NMR data showed that Malten-Pd²⁺ forms even at acidic pH and exists in aqueous solution in a wide range of pH. The mononuclear complex is stable enough not to release Pd²⁺ in solution for a long period of time (at least one week), thus Malten-Pd²⁺, similarly to Maltonis-Pd²⁺, is suitable to be tested in biological analyses. Studies on the U937 cell line revealed that the effect on cell survival reduction induced by Malten is partially lost in Malten-Pd²⁺, while no differences where monitored between the effects of Maltonis-Pd²⁺ and Maltonis, suggesting that the availability of free maltol moieties, that is retained in Maltonis-Pd²⁺, but not in Malten-Pd²⁺, is crucial to guarantee the biological activity of these compounds.