Copper (I) complexes based on novel N, N′-disubstituted thiocarbamides: Synthesis, spectroscopic, in vitro cytotoxicity, DNA damage and G0/G1 cell cycle arrest studies

Abstract

Four trigonal planar copper (I) complexes with novel N, N′-disubstituted isobutoxycarbonyl thiocarbamide ligands were synthesized and characterized by elemental analysis, spectroscopic (FT–IR, 1H and 13C NMR, UV–Visible), TG analysis and single crystal X-ray studies of ligands 1 and 2. The synthesized copper (I) complexes (1a–4a) bear the general formula [Cu(ROCONHCSNHR1)2Cl] where R = –CH2CH(CH3)2 and R1 = 2, 4-dichlorophenyl (1), 2-chloro 4-nitrophenyl (2), 2-methoxyphenyl (3), 4-chloro-2-nitrophenyl (4). All the complexes are mononuclear coordinating through thione sulfur only. Coordination through carbonyl oxygen would have not been possible owing to the presence of strong intramolecular hydrogen bonding (N–H⋯O[dbnd]C) in the ligands. The proposed trigonal planar geometry of complexes has been validated by density functional theory (DFT) study of complex 1a. Computational details of theoretical calculations (DFT) of complex have been discussed. Cyclic voltammogram of complexes 1a–4a displayed quasireversible redox behaviour corresponding to Cu(I)/Cu(II) couple. In vitro cytotoxicity results of ligands and complexes against five human cancer cell lines indicated that all the complexes displayed stronger inhibitory properties than the ligands. The most effective were complexes 3a, 4a and 5a. All the complexes exhibit IC50 values even lower than cisplatin against C13* cell line (cisplatin resistant). The comet assay test of all the complexes against 2008, C13* and IGROV-1 cell lines indicated significant damage to the DNA structure. All the complexes induce apoptosis in 2008, C13* and IGROV-1 cells by blocking cell cycle progression of these cells in G0/G1 phase. © 2019 Elsevier B.V.