Palladium complexes with terpene derivatives of ethylenediamine and benzylamine: Synthesis and study of antitumor properties

• The synthesis of new terpene ligands and palladium complexes is presented. • The study of the toxic effect was carried out on various cell lines of tumor. • Some possible mechanisms of potential antitumor action were analyzed. The synthesis of new terpene ligands and palladium complexes based on them has been described. The stereoselective synthesis of new derivatives (−)-(1 R ,4 S )-camphorquinone and N , N -dimethylethylenediamine ( 1 and 2 ) and palladium chelate complexes ( 3 and 4 ) based on them is presented. It was found that the direct cyclometallation of (1 R ,2 R ,3 R ,5 R )-3-(benzylamino)-2,6,6-trimethylbicyclo[3.1.1]heptane-2-ol ( 5) with palladium acetate leads to the formation of palladacycle 6 . The cytotoxic activity of new ( 3,4,6 ) and previously described ( 7 – 14 ) palladium complexes of various types has been studied. The study of the toxic effect was carried out on various cell lines of tumor origin (pulmonary adenocarcinoma A549, neuroblastoma SH-SY5Y, laryngeal epidermoid Hep-2 and cervical carcinoma HeLa cells). It was found that palladium complexes 6 – 10 with terpene derivatives of benzylamine and a complex 11 with N,N,O-donor terpene ligand have the most pronounced antitumor properties. For 11 the lowest values of the cytotoxic effect IC 50 were found in all cell lines, especially in relation to SH-SY5Y (IC 50 < 0.1 µM). In the course of studying the possible mechanisms of their antineoplastic action, it was found that these substances are able to modulate the processes associated with oxidative stress and have a damaging effect on mitochondria, as well as inhibit the process of HeLa cancer cell glycolysis.