Synthesis, characterization and anticancer potency of novel Mn(II), Co(II), and Cu(II) complexes based on N-[(1E)-1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)ethylidene]-2-(4-methylanilino)acetohydrazide

Metal (II) complexes based on the ligand, N-[(1E)-1-(4-hydroy-6-methyl-2-oxo-2H-pyran-3-yl)ethylidene]-2-(4methylanilino)acetohydrazide (HL) with Co (II), Mn (II), and Cu (II) were successfully synthesized and characterized by the use of analytical, spectral (IR, UV-vis, 1H NMR), and thermal (TGA) measurements. Also, magnetic moment, molar conductance, and electron spin resonance (ESR) spectral assignments for Cu(II) complexes were measured. Moreover, the newly synthesized complexes were tested against Huh-7, HCT-116, A549 cancer cell lines using MTT assay. Their apoptotic activity was determined through flow cytometry using Annexin-V-FITC/PI. Moreover, their ability to arrest cell cycle was studied. Results revealed that the complex of Mn (II) is a high spin octahedral, cobalt (II) complexes are high spin tetrahedral, and copper (II) complexes are square planar. Also, Mn (II), Co (II), and Cu (II) complexes of the ligand showed cytotoxicity activity. The tested complexes showed cytotoxic activity towards three human cancer cell lines, particularly complexes 3 and 5. Complex 3 recorded IC50 values 10.51 mu M and 24.96 mu M, respectively against Huh-7 and A549 cells. Complex 5 showed IC50 values 28.86 mu M and 7.2 mu M, respectively against Huh-7 and A549 cells. Furthermore, results of the Annexin-V-FITC/PI apoptosis assay revealed that compounds could induce apoptosis in cancer cells by increasing the percentage of apoptosis. Complex 3 induces total apoptosis of 37.15% in Huh-7 cells while complex 5 gives 34.15% in A549 cells. Complex 3 gives a significant diminishing of cells in G0/G1 phase in HCT-116 cells, complex 5 caused less accumulation in G0/G1 phase in A549 cells. In conclusion, the new complexes exerted their anticancer activity through induction of apoptosis and cell cycle arrest of cancer cells.