- 期刊
Synthesis, Characterization And Antitumor Activity Of Copper(II) Complexes, [CuL_2] [HL^(1-3)=N,N-DiethyI-N'- (R-Benzoyl)Thiourea (R=H, o-Cl and p-NO_2)]
摘要
The copper(II) complexes of acylthiourea derivatives have been synthesized and characterized by elemental analysis, Ff-IR, FAB(+)-MS, NMR(^1H, ^(13)C), magnetic measurements and cyclic voltammetry. Assessment of antitumor activity against the mouse mammary adenocarcinoma TA3 cell line has demonstrated that all Cu^(II) complexes were more active than their respective ligands and Cu(L^3)_2 showed a higher cytotoxicity than all the compounds tested. Cellular copper accumulation and DNA binding were also determined and the results are consistent with the cytotoxic activities obtained. The copper (II) complexes (CuL_2) were prepared by reaction of Cu(CH_3COO)_2 with the corresponding derivatives of acylthioureas in a Cu:HL molar ratio of 1:2. Acylthiourea ligands, N,N-diethyl-N'-(Rbenzoyl) thiourea (HL^(1-3)) [R=H, o-C1 and p-NO_2] were synthesized in high yield (78-83%) and characterized by elemental analysis, infrared spectroscopy, ^1H and ^(13)C NMR spectroscopy. The complexes CuL_2 were characterized by elemental analysis, IR, FAB(+)-MS, magnetic susceptibility measurements, EPR and cyclic voltammetry. The crystal structure of the complex Cu(L^2)_2 shows a nearly square-planar geometry with two deprotonated ligands (L) coordinated to Cu^(II) 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 (IC_(50) 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 Cu^(II) 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(L^3)_2 in TA3 tumor cells and the much faster binding to cellular DNA than Cu(L^1)_2 are consistent with the in vitro cytotoxic activities found for these copper complexes.
延伸閱讀
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