Synthesis, characterization and ROS-mediated antitumor effects of palladium(II) complexes of curcuminoids

Based on the synthesis of curcumin and its derivatives from aromatic aldehydes, a novel series of palladium(II) complexes with curcumin (or its derivatives) and 2,2'-bipyridine have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of the curcuminoid ligands in H₂O/acetone solution. These complexes have been characterized by ¹H (¹³C) NMR, HRMS and elemental analysis. Crystal structure of 3h has been determined by X-ray diffraction analysis. Their cytotoxicity was tested by MTT. The preliminary results showed that complexes 3d, 3f, 3h have significant inhibition on proliferation of three carcinoma cells such as MCF-7, HeLa and A549 cells, which were more active than cisplatin. Further mechanistic studies indicated that the tested complex 3h arrested the cell cycle in the S phase and can disrupted mitochondrial membrane potential and induced tumor cell apoptosis through reactive oxygen species (ROS)-dependent pathway.