New series of water-soluble thiosemicarbazones and their copper(II) complexes as potentially promising anticancer compounds

New water soluble thiosemicarbazone ligands, namely 3-(3-{[(aminocarbonothioyl) hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H(2)L1Cl), 3-[4-hydroxy-3-({[(methylamino)carbonothioyl]hydrazono}methyl)benzyl]-1-methyl-1H-imidazol-3-ium chloride (H(2)L2Cl) and 3-(3-{[(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H(2)L3Cl) were synthesized through 1:1 condensation reaction of thiosemicarbazide derivatives with 3-(3-formyl-4-hydroxybenzyl)-1-methyl-1H-imidazole-3-ium chloride (Sal(imi)Cl) and characterized by elemental analysis and spectroscopic methods (UV-Vis, H-1 NMR, FTIR). Single crystals of H2L1Cl and H2L2Cl were prepared for crystallographic analysis, which showed similar X-ray structures for both ligands with chiral P2(1)2(1)2(1) space group. The ligands were used for synthesis of the following copper(II) complexes: [Cu(HL1)Cl]Cl, [Cu(HL2)Cl]Cl center dot H2O, and [Cu(HL3)Cl]Cl. All complexes were characterized by physico-chemical and spectroscopic methods. The X-ray structure of [Cu(HL1)Cl]Cl was orthorhombic with Pcba space group while [Cu(HL2)Cl]Cl center dot H2O was triclinic with Pi space group. Both complexes were mononuclear, with tridentate ligands in a thione form. All of the studied compounds showed good solubility and stability in water. The measurement of the molar conductance showed the release of Cl- into solution and substitution of water instead of the coordinated chloride. Among the studied complexes, only [Cu(HL3)Cl]Cl shows a quasi-reversible redox behavior with its reduction and oxidation peak potentials separated by a value of about 0.120 V (E-pc = -0.310 V and E-pa = -0.190 V) indicating one-step and one-electron transfer for Cu-II/Cu-I redox couple. The cytotoxic effect of the compounds was measured using the MTT assay on MCF-7 and K562 cell lines and the results showed that [Cu(HL3)Cl]Cl and H(2)L3Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the MCF-7 cells showed the apoptosis cell death after treating with the H(2)L3Cl and [Cu(HL3)Cl]Cl. Also studies of cell cycles confirmed the cell cycle arrest in G2 phase for H(2)L3Cl and [Cu(HL3)Cl]Cl. (C) 2018 Elsevier B.V. All rights reserved. 2018 Elsevier B.V. All rights reserved.