Imine ligands containing an oxindole moiety, coordinated to essential metals, have been identified as potential good anticancer agents, acting by multifunctional modes, and having their reactivity modulated both by the metal nature and the ligand features.1 In previous studies DNA and mitochondria were identified as main targets of such complexes, in a process occurring by an oxidative mechanism, involving reactive oxygen species (ROS), monitored by different techniques (CD, fluorescence, electrophoresis in gel, viability assays). These complexes act also as good inhibitors of selective proteins (CDK dependent kinases and topoisomerases).2 Further, by using Raman microscopy, it was also verified that lipids were an important target for this class of compounds.3 The main goal here was to verify different coordination motif (N, O or S) in tridentate ligands derived from the endogenous oxindole isatin, coordinated to copper ions, and its influence in interactions with DNA and lipid membranes. Structurally, the complexes are very similar, exhibiting a square planar or slightly distorted geometry, as indicated by EPR data, and complementary DFT calculations. However, the observed order of anticancer activity (IC50 in the range 16 to 40 µM) does not correlate the amount of copper ions inserted into the cells (cervical HeLa cells and fibroblasts P4), after 24h or 48h incubation. Lipid peroxidation followed by fluorescence assays and lipidomics data indicated a significant dependence on structural features of the ligand.
Acknowledgments: FAPESP, CEPID Redoxoma, CNPq.