Synthesis and efficacy of copper(II) complexes bearing N(4)-substituted thiosemicarbazide and diimine co-ligands on plasmid DNA and HeLa cell lines

Abstract

This present work deals with the synthesizes of nine novel thiosemicarbazone copper(II) complexes {[Cu(L)2]Cl C3, [Cu(L)(bpy)]Cl C4?C6, [Cu(L) (phen)]Cl C7?C9 (where, L = H(L1)?H(L3), H(L1) = (E)-N-methyl-2- -(1-phenyl-2-((5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)thio)ethylidene)hydrazinecarbothioamide, H(L2) = (E)-N-ethyl-2-(1-phenyl-2-((5-(pyridin-3-yl)-4H- -1,2,4-triazol-3-yl)thio)ethylidene) hydrazinecarbothioamide, H(L3) = (E)-N- -phenyl-2-(1-phenyl-2-((5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)thio)ethylidene) hydrazinecarbothioamide, bpy = 2,2?-bipyridyl and phen = 1,10-phenanthroline) with improved pharmacological results. The synthesized complexes were characterized by various spectral-analytical techniques. The structure of the copper(II) complexes C1?C9 was proposed by EPR spectroscopy. It confirmed the square planar coordination around Cu(II) complexes. The antibacterial screening of the complexes revealed that complexes C7 and C8 demonstrated significant activity against Gram-positive (B. thuringiensis) and Gram-negative (E. coli) bacteria. The concentration-dependent DNA cleavage activity of supercoiled (SC) pUC18 DNA exhibited complete DNA degradation effect on complex C6 at a minimum concentration of 40 ?M. In vitro cytotoxic results showed that the mixed ligand copper(II) complexes C4, C5 and C7 exhibited higher effects on human cervical cancer cell lines, HeLa, when compared to cisplatin. Hence, the results obtained from each biological screening indicated the superior biological efficacy of the mixed ligand copper(II) complexes bearing diimine moieties. It could be considered as a promising alternative to an existing anticancer drug.