RESUMEN
Diabetes is usually accompanied by increased production of free radicals or impaired antioxidant defenses. The brain is a target tissue of the oxidative attacks caused by diabetes, and there are observed changes in the biochemical parameters of this tissue in the hyperglycemic state. In this study, we aimed to show the effect of N(1)-2,4-dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV) (VOL) compound on diabetic damaged brain tissue, induced by streptozotocin (STZ) on 3.0-3.5-month-old male rats. Single dose of STZ at 65 mg/kg was used to make rats diabetic. Four groups were created randomly. Group (i): control (intact) animals; Group (ii): VOL given control animals; Group (iii): STZ-induced diabetic animals; and Group (iv): orally VOL administered STZ-induced diabetic rats. VOL (0.2 mM/kg/day) administration to control and diabetic animals was performed for a period of 12 days. At the end of day 12, the brain tissues were taken and homogenized. The clear supernatants were used for the determination of glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG), and protein levels. Alanine and aspartate transaminases and acetylcholinesterase (AChE), myeloperoxidase (MPO), xanthine oxidase (XO), and oxidative stress marker enzymes activities were also estimated from the homogenates. According to the obtained results, there is found significant elevation of MDA and NEG levels and activities of transaminases, MPO and XO; whereas the GSH content and the activities of AChE and antioxidant enzymes were strongly decreased in the STZ-induced diabetic brain tissues in comparison to control group animals. Twelve days of administration of VOL complex to the diabetic animals reversed all biochemical parameters significantly in diabetic brain tissues. Our findings suggest that the VOL complex may be an ideal candidate to be used as an anti diabetic agent to improve oxidative injury and protect the brain tissue against damage caused by diabetes. This healing effect of the VOL complex may be due to its antioxidant activity and the insulin-mimetic effects of vanadium.
Asunto(s)
Lesiones Encefálicas , Diabetes Mellitus Experimental , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Glucemia/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glutatión/metabolismo , Peroxidación de Lípido , Masculino , Estrés Oxidativo , Ratas , Estreptozocina/farmacología , TransaminasasRESUMEN
The discovery of new inhibitors that can be used in the treatment of viral diseases, including Covid-19, is an area open to research, and there is a need for innovative compounds with increased efficiency that provide inhibition by suppressing enzyme, and receptor mechanisms. The iron(III) and nickel(II) complexes were synthesized by template condensation of 4-methoxy-salicylaldehyde with S-methylthiosemicarbazone derivatives of 1,1,1-trifluoroacetylacetone (for Fe1) and methylacetoacetate (for Ni1). The complex structures having N2O2-chelating thiosemicarbazidato ligand were identified by analytical, spectroscopic, and X-ray crystallography results. Coordination environment of iron(III) center in complex Fe1 has a distorted square pyramidal geometry consisting of the N2O2 donor set and a chlorine atom, while that of Ni1 is square plane with the set. Inhibitory effect of Fe1 compound against SARS-CoV-2 virus specific 3C-like protease enzyme was investigated experimentally. It was determined that the highest inhibition concentration of Fe1 was 100 µM. Percent inhibition activity at this concentration was on average 30.62 ± 3.809%. Binding of both compounds to the 3C-like protease enzyme specific to the SARS-CoV-2 virus was analyzed using docking calculations. As a result of the docking calculation of Fe1, it has been observed that the compound has a binding energy of -7.4 kcal / mol to 3CL-like protease. It has been observed that the protein amino acids GLY143, THR26, and ASN142 contribute to the high binding affinity of the Fe1. The experimental and theoretical results obtained for the two complexes support each other.
RESUMEN
Diabetes mellitus (DM) is chronic and metabolic disorder, which is mainly attributed by hyperglycemia. Vanadium salts and their oxo-complexes have been shown to possess insulin-mimetic and anti-diabetic activities in animal models and diabetic patients. The main goal of this study was to investigate the protective effect of oxovanadium(IV) complex based on thiosemicarbazone (VOL) [L: (N(1)-2,4-dihydroxybenzylidene-N-(4)-2-hydroxybenzylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV)] on glycoprotein components levels and oxidative lung injury of streptozotocin (STZ)-induced diabetic rats. Male Swiss albino rats were separated into four groups. Group I (n = 5): Control (normal) animals, Group II (n = 5): Control animals administered with VOL, Group III (n = 6): STZ-induced diabetic animals, and Group IV (n = 5): STZ-induced diabetic rats treated with VOL. VOL was given to the experimental animals by gavage at a dose of 0.2 mM/kg body weight every day for 12 days. Diabetes was induced by single intraperitoneal injection of STZ (65 mg/kg body weight). On the 12th day, lung tissue samples were taken. Glycoprotein components, advanced oxidation protein products, protein carbonyl, hydroxyproline levels, and prolidase, arginase, xanthine oxidase, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and adenosine deaminase activities significantly increased whereas aryl esterase, paraoxonase-1, carbonic anhydrase, Na+/K+-ATPase activities remarkably decreased in lung tissue of diabetic rats. Treatment with VOL reversed these effects showing a beneficial effect. The present study shows that VOL has a protective effect against diabetes-induced lung damage as well as on abnormal glycoprotein component levels.
Asunto(s)
Diabetes Mellitus Experimental , Lesión Pulmonar , Tiosemicarbazonas , Animales , Antioxidantes , Glucemia , Diabetes Mellitus Experimental/tratamiento farmacológico , Glicoproteínas , Humanos , Pulmón , Masculino , Estrés Oxidativo , Ratas , Tiosemicarbazonas/uso terapéuticoRESUMEN
Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, 1 H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular OâH···O and CâH···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.
Asunto(s)
Antineoplásicos , Citotoxinas , Tiosemicarbazonas , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Células CACO-2 , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Células HT29 , Células Hep G2 , Humanos , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacocinética , Tiosemicarbazonas/farmacologíaRESUMEN
In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elemental analysis and spectroscopic techniques (UV-visible, IR and 1H NMR). In order to be able to verify the N2O2-type thiosemicarbazidato ligand (L2-) structure in the square planar geometry, complex 1 has been studied as a representative by using single crystal X-ray crystallography. The in vitro cytotoxic activity measurements were carried out in HepG2 and Hep3B hepatocellular carcinomas, HCT116 colorectal carcinoma, and 3 T3 mouse fibroblast cell lines. The palladium complexes exhibited notable cytotoxic activities in all cell lines at lower µM concentrations compared to the standard chemicals, cisplatin and allopurinol. IC50 values were determined between 0.42 ± 0.01 and 12.01 ± 0.37 µg/ml in examining the antixanthine oxidase abilities of the complexes. Two complexes with S-methyl group exhibited a high inhibition activity on the xanthine oxidase. The results indicated that these complexes could be used as active pharmaceutical ingredients.
Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Paladio/farmacología , Tiosemicarbazonas/farmacología , Xantina Oxidasa/antagonistas & inhibidores , Células 3T3 , Animales , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Humanos , Ratones , Paladio/química , Tiosemicarbazonas/químicaRESUMEN
One iron(III) and two manganese(III) complexes based on thiosemicarbazone were synthesized and characterized using analytical and spectroscopic data. The crystallographic analysis showed the square pyramid structures of the complexes. Electronic spectra analysis was performed to determine the nature of the interaction between the complexes and calf thymus DNA (CT-DNA). DNA cleavage activities of the complexes were examined by gel electrophoresis (pBR322 DNA). The cytotoxicity of the complexes was determined against human cervical carcinoma (HeLa) and human colorectal adenocarcinoma (HT-29) cell lines by MTT assay. The results indicated that complex Fe1 is bound to CT-DNA via the intercalation mode, while complexes Mn1 and Mn2 are bound to CT-DNA via groove binding and/or electrostatic interactions rather than the intercalation mode. In addition, they showed good binding activity, which followed the order of Fe1 > Mn2 > Mn1. Complexes were found to promote the cleavage of DNA from supercoiled form (SC, Form I) to nicked circular form (NC, Form II) without concurrent formation of Form III, revealing the single-strand DNA cleavage. No significant cleavage was found in the presence of Mn1 and Mn2; however, it was observed at 2000 and 3000 µM concentrations of Fe1. The ability of Fe1 to cleave DNA was greater than that of other complexes and these results are in conformity with their DNA-binding affinities. Cytotoxicity determination tests revealed that the complex Fe1 on HeLa and HT-29 cells exhibited a higher anti-proliferative effect than Mn1 and Mn2 (Fe1 > Mn2 > Mn1). These studies suggested that the complex Fe1 could be a good candidate as a chemotherapeutic drug targeting DNA.
Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , División del ADN/efectos de los fármacos , ADN/efectos de los fármacos , Tiosemicarbazonas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bovinos , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/química , Humanos , Sustancias Intercalantes/síntesis química , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Hierro/química , Manganeso/química , Estructura Molecular , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/químicaRESUMEN
Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. For comparison, human umbilical vein endothelial cells (HUVECs) was used as a noncancerous cell line. While four of the iron(III) complexes exhibited the antileukemic effect with 50% inhibition of cell growth (IC50 ) values in the 3.4 to 6.9 µg/mL range on K562 cell line, the nickel(II) complexes showed no significant effect on both cell lines. The complexes Fe4, Fe5, and Fe6, bearing 4-methoxy substituent exhibited relatively high antiproliferative activity on both cell lines. Complex Fe3 with 3-methoxy and S-allyl groups exhibited a selectivity between K562 and HUVEC cells by IC50 values of 6.9 and >10 µg/mL, respectively. Lipophilicity, a key parameter for bioavailability and oral administration, was found in the range of -0.3 and +1.3 that desired for drug active ingredients. The results were discussed in the context of a structure-activity relationship.
Asunto(s)
Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Hierro/química , Níquel/química , Tiosemicarbazonas/química , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células K562 , Lípidos/química , Estructura Molecular , Tiosemicarbazonas/síntesis químicaRESUMEN
Thiosemicarbozone complexes that have a broad spectrum of biological activity are formed as a result of condensation reaction between thiosemicarbazide [H2N(C=S)-NH-NH2] and carbonyl-containing compounds. A new Nickel(II) complexes with N1-acetylacetone, N4-4-methoxy-salicylidene-thiosemicarbazidato ligand was synthesized and characterized. We studied the antileukemic activity of the Ni(II) thiosemicarbazone compound and assessed their potential for drug development. Specifically, the effects of this Ni(II) thiosemicarbazone compound on intracellular signal nodes and apoptotic pathways were investigated. According to our results, the Ni(II) thiosemicarbazone compound has apoptotic activity against HL60 cells. Moreover, while Ni(II) thiosemicarbazone compound significantly increased levels of p53 and cleaved caspase-3 proteins, it decreased level of Phospho-Akt1 protein in HL60 cells. The Ni(II) thiosemicarbazone compound could induce HL60 cell apoptosis through inhibiting of PI3K/Akt pathway. These results showed that Ni(II) thiosemicarbozone compound might be an antileukemic agent.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Níquel/administración & dosificación , Semicarbacidas/administración & dosificación , Transducción de Señal/efectos de los fármacos , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Quelantes/análisis , Quelantes/química , Células HL-60 , Humanos , Níquel/química , Semicarbacidas/síntesis químicaRESUMEN
Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings.
Asunto(s)
Antioxidantes , Diabetes Mellitus Experimental , Humanos , Ratas , Masculino , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Corazón , Hipoglucemiantes/uso terapéutico , Estrés Oxidativo , Aorta , Glucemia/metabolismoRESUMEN
New thiosemicarbazone-based zinc(II) complexes were synthesized to study their cytotoxicity on A375 malignant melanoma cells. The complexes containing salicylidene (Zn1a), 3-methoxy-salicylidene (Zn1b) or 4-methoxy-salicylidene (Zn1c) moiety were characterized by analytical and spectroscopic methods. Anticancer potential of the complexes was determined by MTT test and HUVEC endothelial cells line was used to comprehend the effect on normal cells. Zn1b with an IC50 of 13 µM was found to be highly cytotoxic against A375 cancer cells, more effective than cisplatin (IC50: 37 µM). Zn1a and Zn1c did not have a negative effect on cell viability in the normal cells and gave the impression that they are more advantageous than cisplatin in this respect. Further, the ability of Zn1a-c to inhibit neuraminidase enzyme and its role in cytotoxicity was discussed. The test revealed that the Zn1b with 3-methoxy substituent exhibited higher inhibition activity against the neuraminidase than the Zn1a and Zn1c as analogical to the cytotoxicity results. In neuraminidase inhibition, IC50 values of Zn1b and Zn1c were 14 and 66 µM, respectively. These concentrations were very close to the cytotoxicity concentrations for Zn1b and Zn1c. The findings may indicate the role of neuraminidase enzyme inhibition in cell death for Zn1b and Zn1c.
Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Complejos de Coordinación/farmacología , Inhibidores Enzimáticos/farmacología , Neuraminidasa/antagonistas & inhibidores , Tiosemicarbazonas/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Estructura Molecular , Relación Estructura-Actividad , Tiosemicarbazonas/síntesis química , Zinc/químicaRESUMEN
In order to examine the anticancer potential of oxovanadium(IV) complexes with thiosemicarbazone, two new complexes were prepared starting from 2-thenoyltrifluoroacetone-S-methylthiosemicarbazone. The complexes with tetradentate thiosemicarbazone ligand were characterized by elemental analysis, IR, ESI MS, and single-crystal X-ray diffraction analysis. Cytotoxicity on breast cancer cells, MDA-MB-231 and MCF-7, was determined by MTT assay. Cisplatin was positive control and the results were compared with those of the normal cells, HUVEC and 3T3. The complexes exhibited greater activity on cancer cells than cisplatin, but they were cytotoxic at several times higher concentrations in the healthy cells. In our study, the presence of thiophene and fluoro groups in the oxovanadium(IV) complexes with thiosemicarbazone increased greatly the cytotoxic activity of the complexes on breast cancer cells. Moreover, the complexes induced apoptosis-mediated cell death and also reduced the expression of MDR-1 or P-glycoprotein and ABCG2. As a result, the findings indicated that the complexes have selective cytotoxicity on breast cancer cells and can overcome multidrug resistance. These properties of the complexes make it possible to be a potential anticancer drug candidate for breast cancer treatment.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Complejos de Coordinación , Tiosemicarbazonas , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Resistencia a Medicamentos , Femenino , Humanos , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacologíaRESUMEN
A new nickel(II) complex was synthesized by using S-propyl-thiosemicarbazide and 2-amino-3,5-dibromobenzaldehyde. The complex, obtained by the template effect of nickel ions, was structurally analysed by experimental and theoretical vibrational spectroscopy, NMR and density functional theory (DFT) calculations. By using DFT/B3LYP method with 6-311++G(d, p) basis set, the most stable molecular structure of the title molecule was calculated. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the molecule under investigation were determined and compared with the experimental vibrational spectra. The vibrational assignment was achieved using the calculated potential energy distributions of the vibrational modes. Moreover, the molecular electrostatic potential (MEP), the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) energies were calculated, Molecular docking of the molecule was carried out against DNA in order to identify the potential inhibitory action of the title compound. The findings suggested that the aforementioned compound has a strong binding affinity to interact with DNA residues DT8, DC9, DG12, DG16, DA17, and DA18 through the intermolecular hydrogen bonds. Also the performed in silico ADMET analysis was the prediction of the synthesized molecule's pharmacokinetic and toxicity profile expressing good oral drug like actions and non-toxic nature. The complex has been shown to have the possibility to become a model molecule for drug development processes.Communicated by Ramaswamy H. Sarma.
Asunto(s)
Níquel , Tiosemicarbazonas , Espectroscopía de Resonancia Magnética , Conformación Molecular , Simulación del Acoplamiento Molecular , Teoría Cuántica , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , VibraciónRESUMEN
Vanadium compounds are being investigated as potential therapeutic agents in the treatment of many health problems, primarily diabetes. We aimed to provide the effect of N(1)-4-hydroxysalicylidene-N(4)-salicylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV) (VOL) on small intestinal injury in experimental male diabetic rats. Four groups were created of 3.0-3.5-month-old rats. The rats were made diabetic by a single dose of streptozotocin (STZ) at 65 mg/kg and grouped as follows: control animals, VOL-given control animals, STZ-induced diabetic animals and STZ-induced diabetic animals given VOL. A daily dose of 0.2 mM/kg vanadium complex was administered orally for 12 days after the inducement of diabetes. On the 12th day, small intestine tissue samples were taken. According to the data obtained from the biochemical analysis, reduced glutathione (GSH) level, catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), Na+/K+-ATPase and paraoxanase (PON) activities were increased, whereas sialic acid (SA), xanthine oxidase (XO) and disaccharidases (maltase and saccharidase) activities were decreased in the small intestine tissue of VOL-treated diabetic rats. Microscopic examinations revealed a remarkable decrease in the mucosal necrotic areas, discontinuity in the brush border, deterioration of the villi integrity and oedema inside the villi, but with a mild decrease in the inflammatory cells, deterioration and loss of integrity of the gland in the small intestine of VOL-treated diabetic rats. Moreover, VOL treatment markedly decreased the proliferation of villus cells and especially inflammatory cells in the small intestine of diabetic rats. According to the obtained data, the administration of VOL is a potentially convenient strategy to reducing small intestine injury in diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental , Tiosemicarbazonas , Animales , Glucemia , Catalasa/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Glutatión/metabolismo , Intestino Delgado/metabolismo , Masculino , Estrés Oxidativo , Ratas , Estreptozocina , Superóxido Dismutasa/metabolismo , Tiosemicarbazonas/farmacologíaRESUMEN
The S-methyl-thiosemicarbazones of the 2-hydroxy-R-benzaldehyde (R = H, 3-OH 3-OCH(3) or 4-OCH(3)) reacted with the corresponding aldehydes in the presence of FeCl(3) and NiCl(2). New ONNO chelates of iron(III) and nickel(II) with hydroxy- or methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and (1)H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N(1)-4-methoxysalicylidene-N(4)-4-methoxysalicylidene-S-methyl-thiosemicarbazidato-iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 microg/ml (IC(50)) concentrations. Also, some methoxy-substituted nickel(II) chelates exhibit high cytotoxic activity against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings.
Asunto(s)
Quelantes/farmacología , Quelantes del Hierro/farmacología , Níquel/farmacología , Tiosemicarbazonas/farmacología , Línea Celular , Quelantes/síntesis química , Quelantes/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Quelantes del Hierro/síntesis química , Quelantes del Hierro/química , Células K562 , Níquel/química , Relación Estructura-Actividad , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/químicaRESUMEN
Reactions of 2-hydroxy-3-methoxy, 2-hydroxy-4-methoxy-benzaldehyde with 3- and 4-methoxy-substituted salicylaldehyde S-methyl-thiosemicarbazones in the presence of FeCl(3) and NiCl(2) resulted in the corresponding methoxy-substituted N(1),N(4)-diarylidene-S-methyl-thiosemicarbazone chelates. Characterisation of the compounds in the [Fe(L)Cl] and [Ni(L)] general formula was accomplished by means of elemental analysis, conductivity and magnetic measurements, (1)H NMR, UV-vis, IR and mass spectroscopy. Cytotoxicity and proliferation experiments using K562 chronic myeloid leukemia cell line and ECV 304 human endothelial cell line imply that the iron(III) chelates may have anti-leukemic effects with 3.5 microg/dl LD(50) dose.
Asunto(s)
Antineoplásicos/síntesis química , Quelantes/síntesis química , Hierro , Níquel , Compuestos Organometálicos/síntesis química , Tiosemicarbazonas/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular , Quelantes/química , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Férricos/síntesis química , Compuestos Férricos/química , Compuestos Férricos/farmacología , Humanos , Células K562 , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacologíaRESUMEN
5-Chloro-4-methyl-2-hydroxybenzophenone S-propyl-4-phenyl-thiosemicarbazone (H2L) and its cis-dioxomolybdenum(VI) complexes, in the general formula [MoO2(L)R-OH)] (R: methyl, 1; ethyl, 2; n-propyl, 3; n-butyl, 4; n-pentyl, 5), were synthesized and characterized by micro analysis, electronic, infrared and (1)H and (13)C NMR spectra. The crystal structures of complexes, 1 and 3, have been solved by direct methods (SIR92) and refined to the residual indexes R1=0.098 and R1=0.052 respectively. Complexes 1 and 3 are crystallized in the triclinic space group P-1 with Z=2. The crystal study of complex 1 showed the first example of intermolecular hydrogen bond for this type of molybdenum-thiosemicarbazone complexes. The hydrogen bond is between the hydroxyl proton of attached alcohol and an oxo oxygen (in MoO2(2+) unit) of another complex molecule, and its bond distance (1.767(1)Å) is shorter than from the σ-coordination bonds in complex 1. Antioxidant activities of the compounds were determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Ligand showed 23.61% DPPH radical scavenging activity at 250 mg/L concentration. Cupric Reducing Antioxidant Capacity (CUPRAC) was also evaluated and trolox-equivalent antioxidant capacity (TEAC) values were found for ligand, 1 and 3 as 0.51, 0.33 and 0.30 respectively.
Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Quelantes/química , Molibdeno/química , Molibdeno/farmacología , Óxidos/química , Óxidos/farmacología , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/farmacología , Compuestos de Bifenilo/química , Cristalografía por Rayos X , Dimerización , Depuradores de Radicales Libres/química , Enlace de Hidrógeno , Ligandos , Conformación Molecular , Óxidos/síntesis química , Picratos/química , Tiosemicarbazonas/químicaRESUMEN
The nickel(II), iron(III), oxovanadium(IV) complexes of the 3-hydroxysalicylidene-S-methyl-thiosemicarbazone (L) were obtained from the 3-hydroxysalicyldehyde-S-methylthiosemicarbazone with the R1-substituted-salicylaldehyde (R1: H, 3-OH) in the presence of Ni(II), Fe(III), VO(IV) as template ion. The ligand and its complexes were characterized by elemental analysis, electronic, UV/Vis., (1)HNMR, EPR and IR studies. The free ligand and its metal complexes have been tested for in vitro antioxidant capacity by reduction of copper(II) neocuproine (Cu(II)-Nc) using the CUPRAC method. The ligand exhibited more potent in vitro antioxidant capacity than its complexes. The obtained trolox equivalent antioxidant capacity (TEAC) value of the iron(III) complex (TEACCUPRAC=3.27) was higher than those of other complexes. Furthermore, the antioxidant activity of the free ligand and its complexes were determined by in vitro methods measuring the scavenging activity of reactive oxygen species (ROS) including hydroxyl radical (OH), superoxide anion radical (O2(-)), and hydrogen peroxide (H2O2), showing that especially the V(IV) and Fe(III) complexes had significant scavenging activity for ROS.
Asunto(s)
Antioxidantes/síntesis química , Antioxidantes/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Compuestos Férricos/síntesis química , Compuestos Férricos/farmacología , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/farmacología , Elementos de Transición/síntesis química , Vanadatos/síntesis química , Vanadatos/farmacología , Antioxidantes/química , Complejos de Coordinación/química , Compuestos Férricos/química , Depuradores de Radicales Libres/química , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Superóxidos , Tiosemicarbazonas/química , Vanadatos/químicaRESUMEN
The title thiosemicarbazidatodioxouranium(VI) compound was synthesized and characterized by FT-IR, NMR and UV-vis spectroscopies. Solid-state structure of the compound was confirmed by X-ray crystallography. Besides, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-311++G(d,p) basis set for the C, H, Cl, N, O, S atoms and SDD pseudo-potential for the U atom, and compared with the experimental data. Using the TD-DFT method, electronic absorption spectra of the compound have been predicted at same level. As a result, a good agreement is obtained between the experimental and theoretical ones.
Asunto(s)
Modelos Moleculares , Teoría Cuántica , Tiosemicarbazonas/química , Compuestos de Uranio/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Cristalografía por Rayos X , Electrones , Enlace de Hidrógeno , Conformación Molecular , Espectroscopía de Protones por Resonancia Magnética , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , VibraciónRESUMEN
The nickel(II), iron(III) and oxovanadium(IV) complexes of the N2O2 chelating thiosemicarbazones were synthesized using 4-hydroxysalicyladehyde-S-methylthiosemicarbazone and R1-substitute-salicylaldehyde (R1: 4-OH, H) in the presence of Ni(II), Fe(III), VO(IV) ions by the template reaction. The structures of the thiosemicarbazone complexes were characterized by FT-IR, (1)H NMR, elemental, ESI-MS and APCI-MS analysis. The synthesized compounds were screened for their antioxidant capacity by using the cupric reducing antioxidant capacity (CUPRAC) method. Trolox equivalent antioxidant capacity (TEAC) of iron(III) complex, 1c, was measured to be higher than that of the other complexes. Other parameters of antioxidant activity (scavenging effects on â¢OH, O2(â¢-) and H2O2) of these compounds were also determined. All the compounds have shown encouraging ROS scavenging activities.