Synthesis and cytotoxic activity of morpholino-s-triazine derivatives of POCOP-Ni(II) pincers

Six POCOP-Ni(II) complexes (2, 3a, 3b, 4, 5, and 6) bearing a morpholino-s-triazine moiety were synthesized and fully characterized. The structures of complexes 2 and 3a were determined by single-crystal X-ray diffraction, revealing a distorted square-planar geometry around the metal center. Based on these structures, a supramolecular analysis using Hirshfeld surfaces was also carried out, identifying intermolecular hydrogen bonding and π⋯π stacking interactions. The antiproliferative activity of all complexes was evaluated against six cancer cell lines and a non-cancerous cell line (COS7). Complexes 3a and 3b exhibited the highest antiproliferative activity mainly against leukemia (K562), with IC₅₀ values of 0.55 ± 0.04 μM and 0.59 ± 0.04 μM, respectively. A study of the mechanism of action includes competitive displacement of ethidium bromide (EB) fluorescence within DNA, and molecular docking with DNA and PI3K.