Synthesis, Characterization And Antitumor Activity OfCopper(II) Complexes, [CuL₂] [HL^1-3=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(CH3COO)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 characterized by elemental analysis, infrared spectroscopy, 1H and 13C NMR spectroscopy. The complexes CuL2 were characterized by elemental analysis, IR, FAB(+)-MS, magnetic susceptibility measurements, EPR and cyclic voltammetry. The crystal structure of the complex Cu(L2)2 shows a nearly square-planar geometry with two deprotonated ligands (L) coordinated to CuII through the oxygen and sulfur atoms in a cis arrangement. The antitumor activity of the copper(II) complexes with acylthiourea ligands was evaluated in vitro against the mouse 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 that the coordination of the chelate ligands around the CuII enhances the antitumor activity and, furthermore, this result confirmed that the participation of the nitro and chloro substituent groups in the complex activities is slightly relevant. The high accumulation of the complexes Cu(L2)2 and Cu(L3)2 in TA3 tumor cells and the much faster binding to cellular DNA than Cu(L1)2 are consistent with the in vitro cytotoxic activities found for these copper complexes.

Ru(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells

“…The free ligands present an intense band in the region between 1800 and 1610 cm -1 , which is assigned to vC=O stretching vibrations [28,29,55] and is absent in the spectra of the complexes, evidencing …”

“…The complexes exhibit νRu-P stretching in the range 521-511 cm -1 . Also, the νRu-S, νRu-N and νRu-O stretching vibrations occur as weak bands in a region of low intensity at about 500-350 cm -1 [55].3.4 Multinuclear 31 P{ 1 H}, 1 H and 13 C NMR experimentsIn the 1 H NMR spectra of the free ligands, a shoulder band corresponding to a singlet of the N-H group proton is observed in the region of 8.10-8.70 ppm[28,29,50]. This kind of signal is absent in the spectra of the complexes, indicating the deprotonation of the acylthioureide group by the coordination of the ligand, which acts as a monoanionic species, to the metal.…”

Synthesis, characterization and antibacterial activity of nickel (II) and copper (II) complexes of N-(alkyl(aryl)carbamothioyl)-4-nitrobenzamide

“…It has been reported that substituted acylthiourea ligands might act as monodentate sulfur donors, bidentate oxygen and nitrogen donors. They could also coordinate through the keto-or enolthione form, depending of the ligands themselves, and the metal ions and counter-anions used [18][19][20][21][22][23].…”

Preparation, characterization and in vitro antioxidant and cytotoxicity studies of some 2,4-dichloro-N-[di(alkyl/aryl)carbamothioyl] benzamide derivatives

“…Polysubstituted acylthiourea and its fused heterocycle derivatives were utilized as inhibitors of influenza virus [18]. In addition, acylthiourea derivatives and their coordination compounds exhibit strong antitumor and anticancer activity [19]. Benzoylphenylthiourea derivatives possess potent antitumor activity against both pancreatic and prostate cancer cell lines [20].…”