Abstract

The discovery of new coordination compounds with anticancer properties is an active field of research due to the severe side effects of platinum-based compounds currently used in chemotherapy. In the search for new agents for the treatment of cancer, unsymmetrical N2O2-tetradentate ligand (H2L1 and H2L2) and their Ni(II) and Zn(II) asymmetric complexes (Ni-II-L1-2 and Zn-II-L1-2) have been synthesized and fully characterized. H-1 NMR studies revealed that the ligands and complexes were stable in mixtures of DMSO : D2O (9 : 1). Complementary UV-Vis studies confirmed that Zn-II derivatives also exhibit high stability in mixtures DMSO : buffer (6 : 4) after 24 h. Single-crystal X-ray diffraction studies confirmed the molecular structures of H2L1, H2L2, Ni-II-L-1, and (NiII-L2). At the molecular level, complexes were completely planar without significant distortions of the square-planar geometry according to tau(4) parameter. Furthermore, the crystalline structures revealed non-classical intermolecular interactions of the C-H center dot center dot center dot O and the Ni center dot center dot center dot Ni type. The ligands and complexes were screened against the human osteosarcoma (MG-63), human colon cancer (HCT-116), breast cancer (MDA-MB-231) cell lines, and non-cancerous cells (L929). H2L1 and H2L2 ligands not caused cytotoxic effects at a concentration of 100 mu M, while Ni-II-L-2, Zn-II-L-1, and Zn-II-L-2 complexes induce cytotoxic effects in all cell lines. Ni-II-L-2 was a more active complex against MG-63 (3.9 +/- 1.5) and HCT-116 (3.4 +/- 1.7) cell lines with IC50 values in the low micromolar range. In addition, this compound was 10-, 5-, and 11-fold more potent than cisplatin in MG-63 (39 +/- 1.8), HCT-116 (17.2), and MDA-MB-231 (131 +/- 18), respectively. Three complexes exhibited great selectivity for tumoral cells with SI values ranging from 1.6 to 7.4.