Synthesis, characterization and antitumor activity of copper(II) complexes, [CuL2] [HL1-3=N,N-diethyl-N′-(R-benzoyl)thiourea (R=H, o-Cl and p-NO2)]

Abstract

The copper (II) complexes ( CuL2) were prepared by reaction of Cu ( CH3 COO)2 with the corresponding derivatives of acylthioureas in a Cu:HL molar ratio of 1:2. Acylthiourea ligands, N,N-diethyl-N′-(R-benzoyl)thiourea (HL1-3) [R=H, o-Cl and p-NO2] were synthesized in high yield (78-83%) and characterizedby elemental analysis, infrared spectroscopy, 1H and 13C NMR spectroscopy. The complexes CuL2 werecharacterized by elemental analysis, IR, FAB(+)-MS, magnetic susceptibility measurements, EPR and cyclicvoltammetry. The crystal structure of the complex Cu(L2) 2 shows a nearly square-planar geometry with twodeprotonated ligands (L) coordinated to CuII through the oxygen and sulfur atoms in a cis arrangement. Theantitumor activity of the copper(II) complexes with acylthiourea ligands was evaluated in vitro against themouse mammary adenocarcinoma TA3 cell line. These complexes exhibited much higher cytotoxic activity(IC50 values in the range of 3.9-6.9 μM) than their corresponding ligands (40-240 μM), which indicates thatthe coordination of the chelate ligands around the CuII enhances the antitumor activity and, furthermore, thisresult confirmed that the participation of the nitro and chloro substituent groups in the complex activities isslightly relevant. The high accumulation of the complexes Cu(L2)2 and Cu(L3)2 in TA3 tumor cells and themuch faster binding to cellular DNA than Cu(L 1)2 are consistent with the in vitro cytotoxic activities foundfor these copper complexes.