Anticancer activity of Ni( ii ) and Zn( ii ) complexes based on new unsymmetrical salophen-type ligands: synthesis, characterization and single-crystal X-ray diffraction

VILLAMAN, DAVID; VEGA, ANDRÉS; SANTA MARIA DE LA PARRA, LUCÍA; LEÓN, IGNACIO E.; LEVÍN, PEDRO; TORO, PATRICIA M.

DALTON TRANSACTIONS

ROYAL SOC CHEMISTRY

Año: 2023 vol. 52 p. 10855 - 10868

1477-9226

The discovery of new coordination compounds with anticancer properties is an active field of researchdue to the severe side effects of platinum-based compounds currently used in chemotherapy. In thesearch for new agents for the treatment of cancer, unsymmetrical N2O2-tetradentate ligand (HandH2L2) and their Ni(II) and Zn(II) asymmetric complexes (NiII-L1–2and ZnII-L1–2) have been synthesized andfully characterized.1H NMR studies revealed that the ligands and complexes were stable in mixtures ofDMSO : D2O (9 : 1). Complementary UV-Vis studies confirmed that ZnIIderivatives also exhibit high stabilityin mixtures DMSO : buffer (6 : 4) after 24 h. Single-crystal X-ray diffraction studies confirmed the molecularstructures of H2L1, H2L2, NiII-L1, and NiII-L2. At the molecular level, complexes were completelyplanar without significant distortions of the square-planar geometry according to τparameter.Furthermore, the crystalline structures revealed non-classical intermolecular interactions of the C–H⋯Oand the Ni⋯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-cancerouscells (L929). H2L1and H2L2ligands not caused cytotoxic effects at a concentration of 100 μM, while NiL2, ZnII-L1, and ZnII-L2complexes induce cytotoxic effects in all cell lines. NiII-L2was a more activecomplex against MG-63 (3.9 ± 1.5) and HCT-116 (3.4 ± 1.7) cell lines with ICvalues in the low micromolarrange. 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 selectivityfor tumoral cells with SI values ranging from 1.6 to 7.4.5042L1II