Schiff base containing fluorouracil and its M(II) complexes: Synthesis, characterization, cytotoxic and antioxidant activities

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• Cu(II), Ru(II), and Pd(II) complexes were synthesized and characterized by different spectroscopic techniques. • The antioxidant activities of the synthesized compounds were investigated in detail. • The cytotoxicity of the new compounds was investigated in comparison with 5-FU against Caco-2 and L-929 cell lines. • The synthesized compounds alone or in combination with electroporation showed higher cytotoxicity than 5-Fu in the treatment of Caco-2 cancer cells. Herein, new Cu(II), Ru(II) and Pd(II) complexes including (2 E ,2′ Z )-2,2′-(1,2-phenylenebis(azan-1-yl-1-ylidene))bis(5-fluoro-2,3dihydropyrimidin-4(1 H )-one) Schiff base ligand were synthesized and characterized. Cu(II), Ru(II), and Pd(II) metal complexes were characterized through microanalysis, molar conductivity, magnetic susceptibility, mass spectrometer, FT-IR, 1 H– 13 C NMR, UV–Vis, and thermal analysis. The antioxidant activities of the compounds were compared with the results of 5-fluorouracil (5-FU) by using different methods. The synthesized compounds exhibited quite strong activities compared to the parent drug. The cytotoxicity of reference drug 5-FU and the synthesized compounds against human colon cancer cells (Caco-2) and fibroblast cells (L-929) were determined using in vitro MTT assay. In addition, it was investigated whether electroporation (EP) enhanced the anticancer effect of these compounds in the Caco-2 cancer cells. According to the study's findings, the Ru(II) complex showed a low cytotoxic effect (IC 50 : 100.4 µM). However, the new ligand and its Cu(II) and Pd(II) complexes showed a better cytotoxic effect in Caco-2 cells than the reference drug 5-FU. The same compounds (ligand, Cu(II), and Pd(II) complexes) showed 4–9 times lower cytotoxic effect in L-929 healthy fibroblast cells than in cancerous cells. 5-FU, ligand, Cu(II), and Pd(II) compounds used in combination with EP reduced the viability of Caco-2 cancer cells to 45.09%, 42.46%, 38.04%, and 30.85%, respectively. Therefore, the ligand and its Cu(II) and Pd(II) complexes may be promising anticancer agents, especially when used in combination with EP.