RESUMO
Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.
Assuntos
Antineoplásicos , Neoplasias da Mama , DNA , Índio , Naftoquinonas , Humanos , Naftoquinonas/química , Naftoquinonas/farmacologia , Índio/química , Índio/farmacologia , DNA/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Feminino , Ensaios de Seleção de Medicamentos Antitumorais , Cristalografia por Raios X , Células MCF-7 , Modelos Moleculares , Estrutura MolecularRESUMO
The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.
Assuntos
Antineoplásicos , Complexos de Coordenação , Gálio , Gálio/farmacologia , Gálio/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Cisplatino , Índio/química , Diarileptanoides , Linhagem Celular Tumoral , Ligantes , Antineoplásicos/farmacologiaRESUMO
99mTc-EDDA/HYNIC-TOC is an easily available and cheaper radionuclide that could be used for somatostatin-receptor-based imaging of neuroendocrine tumours (NETs). We aimed to evaluate the diagnostic performance of 99mTc-EDDA/HYNIC-TOC compared to111In-DTPA-octreotide in patients (pts) with NETs. We performed a prospective diagnostic study including pts with biopsy-confirmed NET and at least one visible lesion at conventional imaging. Two independent nuclear medicine physicians evaluated pts who underwent 99mTc and 111In scans and images. The primary outcome was comparative diagnostic accuracy of 99mTc and 111In. Secondary outcomes include safety. Nine pts were included and performed 14 paired scans. Overall, 126 lesions were identified. 99mTc demonstrated superior sensitivity both when all images were analysed (93.7, 95% CI 88.1% - 96.8% versus 74.8%, 95% CI 66.6 - 81.6%, p < 0.001) and when liver-specific images were analysed (97.8%, 95% CI 92.7% - 99.5% versus 85.1%, 95% CI 76.6% - 91.0%, p < 0.001). 99mTc was also associated with a lower negative likelihood ratio (LR) (0.002, 95% CI 0.009 - 0.1 versus 0.19, 95% CI 0.12 - 0.42, p = 0.009) when evaluating hepatic lesions. Adverse events happened in 3 pts after 111In and in 2 pts after 99mTc, all grade 1. The 99mTc demonstrated a higher sensitivity overall and a better negative LR in liver-specific images compared to 111In in pts with NETs. Our findings suggest that 99mTc is an alternative to 111In and is especially useful in ruling out liver metastases. NCT02691078.
RESUMO
AIMS: The aim was to develop an electrochemical/optical set-up and correlate it (as validation) with other chemical and physical methods to obtain a simple and cost-effective system to study biofilm formation. METHODS AND RESULTS: A simple microfluidic cell and methods allowed continuous monitoring of the first, critical steps of microbial attachment. We monitored sulfate-reducing bacteria (SRB) at the early stages of biofilm formation. Herein, we studied the formation and adherence of SRB consortium biofilms over an indium tin oxide (ITO) conducting surface using microbiological and chemical methods, microscopic observations [scanning electron microscopy (SEM) and optical], and electrochemical impedance spectroscopy (EIS) measurements. The SRB biofilm formation was evaluated for 30 d by SEM and EIS. Charge transfer resistance decreased when the microbial population colonized the electrode. The monitoring of early-stage biofilm formation was performed using EIS at a single frequency of 1 Hz during the first 36 h. CONCLUSIONS: The simultaneous use of optical, analytical, and microbiological methods allowed us to connect the kinetics of the growth of the microbial consortium to the values obtained via the electrochemical technique. The simple setup we present here can help laboratories with limited resources to study biofilm attachment and facilitates the development of various strategies to control biofilm development in order to avoid damage to metallic structures (microbiologically influenced corrosion, MIC) or the colonization of other industrial structures and medical devices.
Assuntos
Biofilmes , Indicadores e Reagentes/farmacologia , Eletrodos , CorrosãoRESUMO
Gallium and indium octahedral complexes with isoniazid derivative ligands were successfully prepared. The ligands, isonicotinoyl benzoylacetone (H2L1) and 4-chlorobenzoylacetone isonicotinoyl hydrazone (H2L2), and their respective coordination compounds with gallium and indium [GaL1(HL1)] (GaL1), [GaL2(HL2)] (GaL2), [InL1(HL1)] (InL1) and [InL2(HL2)] (InL2) were investigated by NMR, ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction and elemental analysis. In vitro interaction studies with human serum albumin (HSA) evidenced a moderate affinity of all complexes with HSA through spontaneous hydrophobic interactions. The greatest suppression of HSA fluorescence was caused by GaL2 and InL2, which was associated to the higher lipophilicity of H2L2. In vitro interaction studies with CT-DNA indicated weak interactions of the biomolecule with all complexes. Cytotoxicity assays with MCF-7 (breast carcinoma), PC-3 (prostate carcinoma) and RWPE-1 (healthy human prostate epithelial) cell lines showed that complexes with H2L2 are more active and selective against MCF-7, with the greatest cytotoxicity observed for InL2 (IC50 = 10.34 ± 1.69 µM). H2L1 and H2L2 were labelled with gallium-67, and it was verified that 67GaL2 has a greater lipophilicity than 67GaL1, as well as higher stability in human serum or in the presence of apo-transferrin. Cellular uptake assays with 67GaL1 and 67GaL2 evidenced that the H2L2-containing radiocomplex has a higher accumulation in MCF-7 and PC-3 cells than the non-halogenated congener 67GaL1. The anti-Mycobacterium tuberculosis assays revealed that both ligands and metal complexes are potent growth inhibitors, with MIC90 (µg mL-1) values observed from 0.419 ± 0.05 to 1.378 ± 0.21.
Assuntos
Antineoplásicos , Complexos de Coordenação , Gálio , Mycobacterium tuberculosis , Neoplasias , Tuberculose , Masculino , Humanos , Isoniazida/farmacologia , Índio/farmacologia , Gálio/farmacologia , Gálio/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
Polymer inclusion membranes containing cellulose triacetate as support, Ionquest® 801 ((2-ethylhexyl acid) -mono (2-ethylhexyl) phosphonic ester) as extractant, and 2NPOE (o-nitrophenyl octyl ether) or TBEP (tri (2-butoxyethyl phosphate)) as plasticizers were characterized using several instrumental techniques (Fourier Transform Infrared Spectroscopy (FT-IR), Reflection Infrared Mapping Microscopy (RIMM), Electrochemical Impedance Spectroscopy (EIS), Differential Scanning Calorimetry (DSC)) with the aim of determining physical and chemical parameters (structure, electric resistance, dielectric constant, thickness, components' distributions, glass transition temperature, stability) that allow a better comprehension of the role that the plasticizer plays in PIMs designed for In(III) transport. In comparison to TBEP, 2NPOE presents less dispersion and affinity in the PIMs, a plasticizer effect at higher content, higher membrane resistance and less permittivity, and a pronounced drop in the glass transition temperature. However, the increase in permittivity with In (III) sorption is more noticeable and, in general, PIMs with 2NPOE present higher permeability values. These facts indicate that In (III) transport is favored in membranes with chemical environment of high polarity and efficiently plasticized. A drawback is the decrease in stability because of the minor affinity among the components in 2NPOE-PIMs.
RESUMO
The Organisation for Economic Co-operation and Development has listed thirteen engineered nanomaterials (ENM) in order to investigate their toxicity on human health. Silicon dioxide (SiO2) and titanium dioxide (TiO2) are included on that list and we added indium tin oxide (ITO) nanoparticles (NPs) to our study, which is not listed on OECD suggested ENM to be investigated, however ITO NPs has a high potential of industrial production. We evaluate the physicochemical properties of SiO2 NPs (10-20 nm), TiO2 nanofibers (NFs; 3 µm length) and ITO NPs (<50 nm) and the impact of protein-corona formation on cell internalization. Then, we evaluated the toxicity of uncoated ENM on human lung epithelial cells exposed to 10 and 50 µg/cm2 for 24 h. TiO2 NFs showed the highest capability to adsorb proteins onto the particle surface followed by SiO2 NPs and ITO NPs after acellular incubation with fetal bovine serum. The protein adsorption had no impact on Alizarin Red S conjugation, intrinsic properties for reactive oxygen (ROS) formation or cell uptake for all types of ENM. Moreover, TiO2 NFs induced highest cell alterations in human lung epithelial cells exposed to 10 and 50 µg/cm2 while ITO NPs induced moderated cytotoxicity and SiO2 NPs caused even lower cytotoxicity under the same conditions. DNA, proteins and lipids were mainly affected by TiO2 NFs followed by SiO2 NPs with toxic effects in protein and lipids while limited variations were detected after exposure to ITO NPs on spectra analyzed by Fourier Transform Infrared Spectroscopy.
Assuntos
Nanoestruturas/química , Nanoestruturas/toxicidade , Coroa de Proteína/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Tamanho Celular , Grânulos Citoplasmáticos/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Células Epiteliais/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Dióxido de Silício/química , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Propriedades de Superfície , Titânio/química , Titânio/metabolismo , Titânio/toxicidade , Cicatrização/efeitos dos fármacosRESUMO
In this work, an environmentally-friendly leaching process for the recovery of indium (In) and tin (Sn) from LCD panel waste was investigated. Easily degradable citrates (C6H5O73-), i.e., sodium citrate and citric acid, were used as complexing agents. The morphology and composition of the species present in the LCD powder before and after the leaching processes were characterized by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The concentrations of In, Sn, and iron (Fe) present in the leachate were determined by atomic absorption spectrometry (AAS). The necessary thermodynamic conditions for achieving substantial In recovery were established by using MEDUSA software. The optimal process conditions were determined experimentally by varying the initial citrate concentration as well as by using reducing or oxidizing media, respectively hydrazine (N2H4) or hydrogen peroxide (H2O2). It was found that using N2H4 in a citrate solution as a reducing agent enhances the leaching efficiency. However, high concentrations of Sn and Fe with respect to In were found in the LCD powder. Therefore, a pretreatment processes to first remove the excess of Sn and Fe, which compete with In for the citrate, was implemented. Leaching with 1â¯M citrate, 0.2â¯M N2H4, at pHâ¯=â¯5, using sodium hydroxide (NaOH) at solid:liquid (S:L) ratio of 20â¯gâL-1, yielded a remarkably high In recovery of 98.9% after 16.6â¯h.
Assuntos
Resíduo Eletrônico , Cristais Líquidos , Citratos , Ácido Cítrico , Peróxido de Hidrogênio , Índio , Reciclagem , EstanhoRESUMO
Mobile phones are one of the fastest growing types of electronic waste disposed of world-wide. One of the main components in these devices is the LCD (liquid crystal display) panel that contains conductive electrodes made of indium tin oxide. A large amount of In, which is categorized as a critical raw element, has been used to manufacture indium tin oxide films. This study applies laser-induced breakdown spectroscopy (LIBS) for the analysis of LCD samples from mobile phones in order to determine the In content. Both conventional univariate calibration and non-traditional calibration using different transition energies (emission lines), named multi-energy calibration (MEC), were assessed. To evaluate the accuracy of the results, Method EPA 3052 was performed for acid digestion of the samples using microwave-assistance, and the In content was determined by ICP OES. Indium concentrations ranged from 35 to 47â¯mgâ¯kg-1 for all samples evaluated. The results showed the best accuracy for LIBS methods after the spectra were normalized by the carbon line at 193.09â¯nm. The univariate-LIBS model showed a standard error of calibration (SEC) about 10-fold lower than the samples' concentration, LOD and LOQ of 0.3 and 1.0â¯mgâ¯kg-1, respectively. MEC proved to be a fast and efficient alternative for direct solid analysis, and In concentrations were determined by LIBS using only two calibration pellets. The LOD and LOQ for MEC-LIBS method were 2.1 and 7â¯mgâ¯kg-1, respectively.
RESUMO
Electrically active field-effect transistors (FET) based biosensors are of paramount importance in life science applications, as they offer direct, fast, and highly sensitive label-free detection capabilities of several biomolecules of specific interest. In this work, we report a detailed investigation on surface functionalization and covalent immobilization of biomarkers using biocompatible ethanolamine and poly(ethylene glycol) derivate coatings, as compared to the conventional approaches using silica monoliths, in order to substantially increase both the sensitivity and molecular selectivity of nanowire-based FET biosensor platforms. Quantitative fluorescence, atomic and Kelvin probe force microscopy allowed detailed investigation of the homogeneity and density of immobilized biomarkers on different biofunctionalized surfaces. Significantly enhanced binding specificity, biomarker density, and target biomolecule capture efficiency were thus achieved for DNA as well as for proteins from pathogens. This optimized functionalization methodology was applied to InP nanowires that due to their low surface recombination rates were used as new active transducers for biosensors. The developed devices provide ultrahigh label-free detection sensitivities â¼1 fM for specific DNA sequences, measured via the net change in device electrical resistance. Similar levels of ultrasensitive detection of â¼6 fM were achieved for a Chagas Disease protein marker (IBMP8-1). The developed InP nanowire biosensor provides thus a qualified tool for detection of the chronic infection stage of this disease, leading to improved diagnosis and control of spread. These methodological developments are expected to substantially enhance the chemical robustness, diagnostic reliability, detection sensitivity, and biomarker selectivity for current and future biosensing devices.