RESUMO
The interaction of a multi-component system consisting of benzene-1,4-diyldimethanimine-bridged dimeric zinc-phthalocyanine groups (4OMPCZ) with calf thymus DNA (ct-DNA) was investigated using UV-Vis absorption, fluorescence emission spectroscopy methods, and viscosity measurements. The binding constant, Kb, which is an important parameter to gain information about the binding mode, was found as 9.7 × 107 M-1 from the UV-Vis absorption studies. Another important spectrophotometric tool is competitive displacement assays with Ethidium bromide and Hoechst 33342. Through this experiment, a higher KSV value was obtained with Hoechst for the phthalocyanine derivative, 4OMPCZ, and the ct-DNA complex than with ethidium bromide. Additionally, molecular docking studies were conducted to calculate the theoretical binding constant and visualize the interactions of 4OMPCZ with a model DNA. According to docking results, although the interactions are mainly located in the major groove of the DNA helix, due to the wrapping, these interactions can also be extended to the minor groove of the DNA. Spectrophotometric, molecular docking, and viscosity studies revealed that the interaction of 4OMPCZ with DNA is likely to be via the major and minor grooves. The in vitro cytotoxic activity of 4OMPCZ was evaluated by MTT assay on human colon cancer cells (HT29) after 72 h of treatment. 4OMPCZ indicated significant cytotoxic activity when stimulated with UV light compared to the standard chemotherapy drugs, fluorouracil (5-FU), and cisplatin on HT29 colon cancer cells. The IC50 value of 4OMPCZ displayed considerably lower concentrations compared to the standard drugs, 5-FU, and cisplatin.
Assuntos
Antineoplásicos , Neoplasias do Colo , Humanos , Simulação de Acoplamento Molecular , Etídio , Cisplatino , Zinco/farmacologia , Dicroísmo Circular , DNA/química , Antineoplásicos/farmacologia , Espectrometria de Fluorescência , Fluoruracila , Neoplasias do Colo/tratamento farmacológico , Termodinâmica , Viscosidade , Espectrofotometria UltravioletaRESUMO
Carboplatin (CP), a platinum analog, is one of the most widely used chemotherapeutic agents in the treatment of colorectal cancer. Although platinum-based drugs are quite effective in anticancer treatments, their use in a wide spectrum and effective treatment possibilities are limited due to their systemic side effects and drug resistance development. In recent years, studies have focused on increasing the therapeutic efficacy of platinum-based drugs with drug delivery systems. Gelatin, a protein, obtained by the hydrolysis of collagen, is a biocompatible and biodegradable material that can be used in nano drug delivery systems. In this study, CP-loaded gelatin-based NPs (CP-NPs) were exposed to IR light in different temperatures at 30, 35, 40, 45, and 50 °C and characterized by FESEM-EDX, FTIR, UV-Vis, DLS. Accordingly, we synthesized gelatin-based CP-NPs of different sizes between 10-290 nm by exposure to IR. We found that CP-NPs-50, 16 nm nano-sized, obtained at 50 °C had the most cytotoxicity and was 2.2 times more effective than the free drug in HCT 116 colon cancer cells. Moreover, we showed that the cytotoxicity of CP-NPs-50 in normal HUVEC cells was lower. Additionally, we demonstrated that CP-NPs enhanced apoptotic activity while not developing MDR1-related resistance in colon cancer cells. In this study, for the first time drug loaded gelatin-based nanoparticles were synthesized in different sizes with a newly self-assembly method by exposing them to infrared light at different temperatures and their anticancer effects were evaluated subsequently.
Assuntos
Antineoplásicos , Neoplasias do Colo , Nanopartículas , Antineoplásicos/farmacologia , Carboplatina/farmacologia , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Gelatina , HumanosRESUMO
AIM: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3- thiosemicarbazone derivatives. These compounds could be promising anticancer agents in leukemia treatment. BACKGROUND: Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to nonspecificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life. METHODS: In this study, the anticancer effects of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives (A-L) were investigated in chronic myelogenous leukemia K562, Burkitt's lymphoma P3HR1, acute promyelocytic leukemia HL60 cells, and vincristine-resistant sublines of K562 and P3HR1 cells. Additionally, the compounds were tested on lymphoid-derived cells from ALL patients. In order to investigate the particular mechanism of death caused by the cytotoxic effects of the compounds, immunohistochemical caspase 3 staining was performed in P3HR1 cells, and the resulting apoptotic activities were demonstrated. RESULTS: All tested compounds have been found to have cytotoxic effects against lymphoma cells at submicromolar concentrations (IC50= 0.89-1.80 µM). Most compounds show significant selectivity for the P3HR1 and P3HR1 Vin resistance. The most effective and selective compound is 4-bromophenyl substituted compound I (IC50=0.96 and 0.89 µM). Cyclohexyl and benzyl substituted compounds D and E have also been found to have cytotoxic effects against K562 cell lines (IC50=2.38 µM), while the allyl substituted compound C is effective on all cell lines (IC50=1.13-2.21 µM). 4-Fluorophenyl substituted F compound has been observed to be effective on all cells (IC50=1.00-2.41 µM) except K562 cell. Compound C is the only compound that shows inhibition of HL-60 cells (IC50= 1.13 µM). Additionally, all compounds exhibited cytotoxic effects on lymphoidderived cells at 1µM concentration. These results are in accordance with the results obtained in lymphoma cells. CONCLUSION: All compounds tested have submicromolar concentrations of cytotoxic effects on cells. These compounds hold potential for use in future treatments of leukemia.
Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Tiossemicarbazonas/farmacologia , Adolescente , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Indóis/síntese química , Indóis/química , Masculino , Estrutura Molecular , Relação Estrutura-Atividade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Células Tumorais CultivadasRESUMO
Diabetic wounds have a slow healing process and easy to be infected. In addition to current drug treatments, supportive approaches are needed for diabetic wound treatment. In this study, we aimed to load Aloe Vera (AV) and Hypericum perforatum oil (HPO) with PCL/Ge (Poly (É-caprolactone)/Gelatine) polymeric biodegradable by electrospinning method into nanofiber dressings on an experimental diabetic wound model to compare the diabetic wound healing effect. Changes in the amount and chemical structure of phospholipids, proteins, and lipids were investigated in the blood and serum samples of the animals using Fourier transform infrared (FTIR) analysis. To evaluate biological events associated with the wound repair process in inflammatory phase we used oxidant and antioxidant status to determine the healing status of wounds such as Total antioxidant status (TAS), Total oxidant level (TOS) and tumor necrosis factor alpha (TNF-α) levels. TOS level increased in DM groups and decreased in the AV and HPO group. Oxidative stress index decreased and TNF-α level increased in the HPO group. FTIR spectra showed changes in the phospholipids, proteins, and carbon chain of lipids in the whole blood as well as serum of DM rats. FTIR spectra combined with Principal component analysis (PCA) showed, that treated DM rats by AV and HPO caused return chemical structure of blood and serum to this observed in control group. Higher similarity with control group for HPO rats was observed. HPO is better than AV in the alternative for healing on diabetic wound. Thus, we have demonstrated that IR spectroscopy and multivariate data analysis and biochemical assays are consistent and correlative with each other.
Assuntos
Aloe , Diabetes Mellitus , Hypericum , Nanofibras , Animais , Bandagens , Ratos , CicatrizaçãoRESUMO
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.
Assuntos
Antineoplásicos , Citotoxinas , Tiossemicarbazonas , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Células CACO-2 , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HT29 , Células Hep G2 , Humanos , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacocinética , Tiossemicarbazonas/farmacologiaRESUMO
BACKGROUND: The effect of Aloctin, a lectin purified from Aloe vera leaves, and aloe emodin an anthraquinone glycoside purified from the leaves of the same plant, on several cancer cell lines was investigated. METHODS: Aloctin was isolated from A. vera leaf skin by ammonium sulphate precipitation and CNBr-Sepharose 4B-ovalbumin affinity chromatography. Specific new ligands for Aloctin were detected as fetuin and avidin by hemagglutination inhibition tests. The cytotoxic effect of Aloctin and aloe emodin on various human cancer cell lines was tested using MTT assay. Imatinib was tested as standard positive control. The mechanism underlying was tested by the Annexin V-FITC/PI test, with flow cytometry. RESULTS: The most sensitive cells to Aloctin and aloe emodin treatment, were identified as AGS human gastric adenocarcinoma cells. The effect was concentration dependent. It was shown that this effect does not occur by apoptosis or necrosis. In Aloctin-imatinib combinations studies, Aloctin significantly increased the cytotoxic effect of imatinib in a dose-dependent manner. It is expected that the results of this study will reveal important findings for the future use of A. vera lectin as well as aloe emodin in cancer research and contribution to lectin biochemistry.
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Assuntos
Aloe/química , Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Lectinas/farmacologia , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Folhas de Planta/químicaRESUMO
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.
Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Ferro/química , Níquel/química , Tiossemicarbazonas/química , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Células Endoteliais da Veia Umbilical Humana , Humanos , Células K562 , Lipídeos/química , Estrutura Molecular , Tiossemicarbazonas/síntese químicaRESUMO
Haematopoietic stem cells can self-renew and produce progenitor cells, which have a high proliferation capacity. Chemotherapeutic drugs are toxic to normal cells as well as cancer cells, and glucocorticoids (GCs), which are essential drugs for many chemotherapeutic protocols, efficiently induce apoptosis not only in malignant cells but also in normal haematopoietic cells. Studies have shown that haematopoietic cytokines can prevent the apoptosis induced by chemotherapy and decrease the toxic effects of these drugs. However, the apoptosis induction mechanism of GCs in CD34+ haematopoietic cells and the anti-apoptotic effects of cytokines have not been well elucidated. In this study, we investigated the apoptotic effects of GCs on CD34+, a haematopoietic stem/progenitor cell (HSPC) population, and demonstrated the protective effects of haematopoietic cytokines. We used a cytokine cocktail containing early-acting cytokines, namely, interleukin-3 (IL-3), thrombopoietin, stem cell factor and flt3/flk2 ligand, and dexamethasone and prednisolone were used as GCs. Apoptotic mechanisms were assessed by immunohistochemical staining and quantified using H-scoring. Dexamethasone and prednisolone induced apoptosis in CD34+ HSPCs. GC treatment caused a significant increase in apoptotic Fas, caspase-3, cytochrome c and Bax, but a significant decrease in anti-apoptotic Bcl-2. Furthermore, as expected, cytokines caused a significant decrease in all apoptotic markers and a significant increase in Bcl-2. Thus, our findings suggest that CD34+ HSPCs are an extremely sensitive target for GCs and that cytokines protect these cells from GC-induced apoptosis.
RESUMO
In this study, one of the most promising methods of tailoring a composite scaffold material in nano sized diameters, electrospinning method were used to produce Polycaprolactone (PCL)/Graphene Oxide (GO)/Iron(II, III) Oxide (Fe3O4) nanocomposite fibers as biocompatible scaffolds for biomedical applications. Products were analyzed by scanning electron microscopy (SEM) for morphological analysis of the electrospun nanocomposites and Fourier Transform Infrared Spectroscopy (FTIR) was used to determine functional groups of the PCL, GO, and Fe3O4 materials in the electrospun nanocomposites. For physical properties, viscosity, density, permittivity, dielectric loss and liquid and solid state alternating current conductivity, measurements were done for each nanocomposite fibers. Effects of concentration percentage of GO on permittivity, dielectric loss and AC conductivity have been analyzed by using measured and calculated data. Trend lines have been drawn for permittivity, dielectric loss and conductivity via concentration percentage of GO. The relation between ac conductivity and frequency have been studied for each concentration percentage of GO and interpretations have been done by using the obtained results.
Assuntos
Tecnologia Biomédica/métodos , Compostos Férricos/química , Grafite/química , Nanocompostos/química , Poliésteres/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Camundongos , Células NIH 3T3 , Nanocompostos/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Resistência à Tração , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
BACKGROUND: Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. METHODS: Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). RESULTS: 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively). CONCLUSION: This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.
Assuntos
Ligas Dentárias , Hipersensibilidade Imediata/induzido quimicamente , Leucócitos Mononucleares/efeitos dos fármacos , Níquel/imunologia , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Hipersensibilidade Imediata/imunologia , Testes Intradérmicos , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Pele/imunologiaRESUMO
PURPOSE: We aimed to evaluate the influence of current antifibrotic agents as well as the possible results obtained by combining these agents. This study included α-tocopherol, a strong antifibrotic and an efficient neuromediator of pathways used by other agents. MATERIALS AND METHODS: Mitochondrial Bcl-2, Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect patterns, mitosis and cellular reactions due to α-tocopherol alone or combined with paclitaxel, mitomycin C and 5-flurouracil (5-FU), was studied in series obtained from human endothelial and primary Tenon's fibroblast cell cultures. RESULTS: The strongest apoptotic effect in both cell groups belonged to paclitaxel, followed by mitomycin C, and despite the overall suppressive effect of the α-tocopherol combination, mitomycin C increased its efficiency on the endothelial cells. The apoptosis/necrosis ratio was highest in α-tocopherol and lowest in paclitaxel, with α-tocopherol generally decreasing necrosis. Bax was observed at a high level with mitomycin C. Cytotoxicity was the highest with paclitaxel, and the caspase-3 reaction was markedly higher with mitomycin C in both cell types. In the α-tocopherol and 5-FU slides, mitosis and a layered formation were observed. The addition of α-tocopherol reduced the cytotoxicity of all antifibrotic agents in both cell series by decreasing the cell numbers, leading to necrosis. CONCLUSIONS: Alone or in combination, the use of α-tocopherol and 5-FU is safer than other agents. By suppressing the cytotoxic effects of other antifibrotic agents, α-tocopherol is a promising drug for improving the effects of antifibrotics in many aspects of medicine. In addition, it has the potential to play a role beyond its antioxidant and antifibrotic activity in ocular surgery.
Assuntos
Alquilantes/farmacologia , Antioxidantes/farmacologia , Fibroblastos/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Cápsula de Tenon/citologia , alfa-Tocoferol/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Combinação de Medicamentos , Fibroblastos/metabolismo , Fibroblastos/patologia , Citometria de Fluxo , Fluoruracila/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mitomicina/farmacologia , Necrose , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration.
Assuntos
Ligas Dentárias/efeitos adversos , Edema Laríngeo/induzido quimicamente , Níquel/efeitos adversos , Adulto , Feminino , HumanosRESUMO
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.
Assuntos
Quelantes/farmacologia , Quelantes de Ferro/farmacologia , Níquel/farmacologia , Tiossemicarbazonas/farmacologia , Linhagem Celular , Quelantes/síntese química , Quelantes/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Quelantes de Ferro/síntese química , Quelantes de Ferro/química , Células K562 , Níquel/química , Relação Estrutura-Atividade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/químicaRESUMO
An experimental approach to increasing the effectiveness of leukemia treatment with S-phase-specific cytotoxics is to increase the cycling of leukemia cells with growth factors. However, growth factors may have a different relationship with non-cell-cycle-specific agents. The authors examined the effects of granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interferon-alpha (INF-alpha) on the cytotoxic effects of the alkylating agent busulfan on the erythro-myeloid cell line K562. G-CSF and GM-CSF increased the proliferation and colony-forming ability of K562 cells and protected the cells from busulfan effects. INF-alpha decreased the colony-forming ability and proliferation of the K562 cells and demonstrated a possibly additive effect with busulfan. In the cell line K562, the growth factors G-CSF and GM-CSF protected the cells from the non-cell-cycle-specific alkylating agent busulfan, whereas IFN-alpha demonstrated an additive cytotoxic effect.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Bussulfano/toxicidade , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Interferon-alfa/farmacologia , Ensaio de Unidades Formadoras de Colônias , Humanos , Células K562/efeitos dos fármacosRESUMO
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.
Assuntos
Antineoplásicos/síntese química , Quelantes/síntese química , Ferro , Níquel , Compostos Organometálicos/síntese química , Tiossemicarbazonas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Quelantes/química , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/farmacologia , Humanos , Células K562 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologiaRESUMO
In this study, the in vitro effects of vitamin C and selenium on natural killer (NK) cell activity of ss-thalassemia major patients was investigated. At first, significant decreased NK activity was found at E:T ratios of 1:1, 5:1, and 10:1 in whole thalassemia patients. Low-dose selenium treatment enhanced NK activity in patients but there was no change in the control group. High-dose selenium decreased NK activity significantly in splenectomized patients. Different doses vitamin C enhanced NK activity significantly in both splenectomized and unsplenectomized patients. According to these results, selenium dosage should be arranged carefully in thalassemia patients, whereas vitamin C can be used confidently.