RESUMO
Two complexes of Zn(II) and Ni(II) ions with the urea derivative, 2-benzimidazolyl-urea (BZIMU), of formulae [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) were synthesized and characterized by their melting point, elemental analysis, spectroscopic techniques (FTIR, UV-Vis and 1H-NMR), High-resolution mass spectroscopy (HRMS), molar conductivity and thermogravimetric analysis. The crystal structures of 1-2 were determined by X-ray diffraction analysis. The antiproliferative activity of 1-2 was tested in vitro against human adenocarcinoma cell lines: cervix (HeLa) and breast (MCF-7). Their toxicity was surveyed against normal human fetal lung fibroblast cells (MRC-5). The bioactivity mechanism of 1-2 and their related analogues of copper and silver metallodrugs are rationalized by the means of computations. The antimicrobial activity of 1-2 against Escherichia coli (E. coli) is also evaluated. The complexes [ZnBZIMU)2(H2O)](NO3)2 (1) and [Ni(BZIMU)2(CH3CH2OH)2](NO3)2 (2) (BZIMU= 2-Benzimidazolyl-urea), were tested in vitro against HeLa and MCF-7 cells. Their toxicity was surveyed against normal MRC-5 cells. The association of the microbiota with the antiproliferative activity of 1-2 was investigated against Escherichia coli.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Níquel/química , Ureia/análogos & derivados , Ureia/química , Zinco/química , Complexos de Coordenação/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Ligação de Hidrogênio , Bicamadas Lipídicas , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Análise EspectralRESUMO
Direct reaction of copper(I) halides with triphenylstibine (tpSb) and 2-mercapto-thiazolidine (tzdtH) in 1:1:1 molar ratio, results in the formation of the [CuX(µ2-S)-tzdtH)(tpSb)]2 (X=Cl (1), Br (2) and I (3)) complexes. The complexes have been characterized by melting point, FT-IR, UV-vis, (1)H NMR spectroscopic data and X-ray crystallography. Complexes 1-3 are di-nuclear and they are the first examples of mixed metals (CuSb), mixed ligand (thioamide, stibine and halogen) containing complexes. Two µ2-S (1-3) atoms bridge the two copper(I) ions with tetrahedral geometry. The coordination sphere around copper atoms is completed by one Sb from tpSb and one halogen (chlorine, bromine or iodine) atom. Intermolecular via N-Hâ¯X (Cl (1) and Br (2)) interactions stabilized the assembly. The short coppercopper bond distances of 3.103 (1), 3.061 (2) and 3.110, 3.108 (3) Ǻ found in 1-3 indicates d(10)-d(10) interaction between metal centers. The complexes exhibit high photo-sensitivity to UVB light. The complexes 1-3 and the already known [Cu(µ2-I)(tpSb)2]2 (4) were tested for their in vitro cytotoxic activity against human cancer cell lines: MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, estrogen receptor (ER) negative) and MRC-5 (normal human fetal lung fibroblast cells) with sulforhodamine B (SRB) colorimetric assay. Since estrogen receptors (ERs) are located in MCF-7, in contrast to MDA-MB-231 cells, the estrogenic effect of 1-4 on MCF-7 cells was studied by the mean of methylene blue assay. Compound 4 exhibits the highest estrogenic effect. None of 1-4 exceeds the activity of cisplatin against MCF-7 cells, but they are more active than cisplatin towards MDA-MB-231 cells. UVB light increases the effectiveness of complexes on MCF-7 cells which in the case of 4 is up to 28% higher than the corresponding initial complex (without irradiation).