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1.
Luminescence ; 39(6): e4799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858760

RESUMO

In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, Mn3O4, SnO2) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Telúrio , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Telúrio/química , Telúrio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Catálise , Nanopartículas Metálicas/química , Escherichia coli/efeitos dos fármacos , Processos Fotoquímicos , Azul de Metileno/química , Azul de Metileno/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Manganês/química , Manganês/farmacologia , Estanho/química , Estanho/farmacologia , Tamanho da Partícula , Óxidos/química , Óxidos/farmacologia
2.
Appl Environ Microbiol ; 90(6): e0228323, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38757978

RESUMO

Resistance to potassium tellurite (PT) is an important indicator in isolating Shiga toxin-producing Escherichia coli (STEC) O157:H7 and other major STEC serogroups. Common resistance determinant genes are encoded in the ter gene cluster. We found an O157:H7 isolate that does not harbor ter but is resistant to PT. One nonsynonymous mutation was found in another PT resistance gene, tehA, through whole-genome sequence analyses. To elucidate the contribution of this mutation to PT resistance, complementation of tehA and the related gene tehB in isogenic strains and quantitative RT‒PCR were performed. The results indicated that the point mutation not only changed an amino acid of tehA, but also was positioned on a putative internal promoter of tehB and increased PT resistance by elevating tehB mRNA expression. Meanwhile, the amino acid change in tehA had negligible impact on the PT resistance. Comprehensive screening revealed that 2.3% of O157:H7 isolates in Japan did not harbor the ter gene cluster, but the same mutation in tehA was not found. These results suggested that PT resistance in E. coli can be enhanced through one mutational event even in ter-negative strains. IMPORTANCE: Selective agents are important for isolating Shiga toxin-producing Escherichia coli (STEC) because the undesirable growth of microflora should be inhibited. Potassium tellurite (PT) is a common selective agent for major STEC serotypes. In this study, we found a novel variant of PT resistance genes, tehAB, in STEC O157:H7. Molecular experiments clearly showed that one point mutation in a predicted internal promoter region of tehB upregulated the expression of the gene and consequently led to increased resistance to PT. Because tehAB genes are ubiquitous across E. coli, these results provide universal insight into PT resistance in this species.


Assuntos
Escherichia coli O157 , Proteínas de Escherichia coli , Regiões Promotoras Genéticas , Telúrio , Telúrio/farmacologia , Escherichia coli O157/genética , Escherichia coli O157/efeitos dos fármacos , Proteínas de Escherichia coli/genética , Farmacorresistência Bacteriana/genética , Mutação , Antibacterianos/farmacologia , Japão
3.
NanoImpact ; 34: 100505, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579989

RESUMO

The increasing application of quantum dots (QDs) increases interactions with organisms. The inflammatory imbalance is a significant manifestation of immunotoxicity. Macrophages maintain inflammatory homeostasis. Using macrophages differentiated by phorbol 12-myristate 13-acetate-induced THP-1 cells as models, the study found that low-dose (5 µM) cadmium telluride QDs (CdTe-QDs) hindered monocyte-macrophage differentiation. CD11b is a surface marker of macrophage, and the addition of CdTe-QDs during induction resulted in a decrease in CD11b expression. Moreover, exposure of differentiated THP-1 macrophage (dTHP-1) to 5 µM CdTe-QDs led to the initiation of M1 polarization. This was indicated by the increased surface marker CD86 expression, along with elevated level of NF-κB and IL-1ß proteins. The potential mechanisms are being explored. The transcription factor EB (TFEB) plays a significant role in immune regulation and serves as a crucial regulator of the autophagic lysosomal pathway. After exposed to CdTe-QDs, TFEB activation-mediated autophagy and M1 polarization were observed to occur simultaneously in dTHP-1. The mTOR signaling pathway contributed to TFEB activation induced by CdTe-QDs. However, mTOR-independent activation of TFEB failed to promote M1 polarization. These results suggest that mTOR-TFEB is an advantageous target to enhance the biocompatibility of CdTe-QDs.


Assuntos
Compostos de Cádmio , Macrófagos , Pontos Quânticos , Serina-Treonina Quinases TOR , Telúrio , Telúrio/farmacologia , Compostos de Cádmio/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Células THP-1 , Autofagia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
4.
Folia Microbiol (Praha) ; 69(2): 433-444, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38261148

RESUMO

Tellurite resistance gene clusters have been identified in numerous pathogenic bacteria, including clinical isolates of Escherichia coli. The rareness of tellurium in host organisms and the noncontaminated environment raises a question about the true functionality of tellurite resistance gene clusters in pathogenesis and their possible contribution to bacterial fitness. The study aims to point out the beneficial effects of the tellurite resistance gene cluster of pathogenic bacteria to survive in ROS-rich environments. Here, we analysed the bacterial response to oxidative stress conditions with and without tellurite resistance gene clusters, which are composed of terWY1XY2Y3 and terZABCDEF genes. By measuring the levels of protein carbonylation, lipid peroxidation, and expression changes of oxidative stress genes upon oxidative stress, we propose a tellurite resistance gene cluster contribution to the elimination of oxidative damage, potentially increasing fitness and resistance to reactive oxygen species during macrophage attack. We have shown a different beneficial effect of various truncated versions of the tellurite resistance gene cluster on cell survival. The terBCDEF genes increased the survival of E. coli strain MC4100 by 13.21%, terW and terZABCDEF by 10.09%, and terWY1XY2Y3 and terZABCDEF by 25.57%, respectively. The ability to survive tellurite treatment is the most significant at 44.8% in wild clinical strain KL53 compared to laboratory strain E. coli MC4100 due to a complete wild-type plasmid presence.


Assuntos
Escherichia coli , Telúrio , Telúrio/farmacologia , Telúrio/metabolismo , Estresse Oxidativo , Família Multigênica
5.
ACS Appl Mater Interfaces ; 15(46): 53827-53834, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37944101

RESUMO

Antibacterial nanoagents with well-controlled structures are greatly desired to address the challenges of bacterial infections. In this study, a featherlike tellurium-selenium heterostructural nanoadjuvant (TeSe HNDs) was created. TeSe HNDs produced 1O2 and had high photothermal conversion efficiency when stimulated with 808 nm near-infrared (NIR) light. To create a synergistic treatment system (TeSe-ICG) with better photothermal and photodynamic capabilities, the photosensitizer indocyanine green (ICG) was then added. With a bactericidal rate of more than 99%, the NIR-mediated TeSe-ICG demonstrated an efficient bactericidal action against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). In addition, TeSe-ICG was also effective in treating wound infections and could effectively promote wound healing without obvious toxic side effects. In conclusion, TeSe-ICG is expected to be a good candidate for the treatment of bacterial infections.


Assuntos
Fotoquimioterapia , Selênio , Infecções Estafilocócicas , Humanos , Selênio/farmacologia , Telúrio/farmacologia , Fototerapia , Verde de Indocianina/química , Escherichia coli , Antibacterianos/farmacologia
6.
Environ Res ; 226: 115659, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906266

RESUMO

Allium sativum (A. sativum)is well known for its therapeutic and culinary uses. Because of their high medicinal properties, the clove extract was selected to synthesize cobalt-tellurium nanoparticles. The aim of the study was to evaluate the protective activity of the nanofabricated cobalt-tellurium using A. sativum (Co-Tel-As-NPs) against H2O2-induced oxidative damage in HaCaT cells. Synthesized Co-Tel-As-NPs were analyzed using UV-Visible spectroscopy, FT-IR, EDAX, XRD, DLS, and SEM. Various concentrations of Co-Tel-As-NPs were used as a pretreatment on HaCaT cells before H2O2 was added. Then, the cell viability and mitochondrial damage were compared between pretreated and untreated control cells using an array of assays (MTT, LDH, DAPI, MMP, and TEM), and the intracellular ROS, NO, and antioxidant enzyme production were examined. In the present research, Co-Tel-As-NPs at different concentrations (0.5, 1.0, 2.0, and 4.0µg/mL) were tested for toxicity using HaCaT cells. Furthermore, the effect of H2O2 on the viability of HaCaT cells was evaluated using the MTT assay for Co-Tel-As-NPs. Among those, Co-Tel-As-NPs at 4.0 µg/mL showed notable protection; with the same treatment, cell viability was discovered to be 91% and LDH leakage was also significantly decreased. Additionally, the measurement of mitochondrial membrane potential was significantly decreased by Co-Tel-As-NPs pretreatment against H2O2. The recovery of the condensed and fragmented nuclei brought about by the action of Co-Tel-As-NPs was identified using DAPI staining. TEM examination of the HaCaT cells revealed that the Co-Tel-As-NPs had a therapeutic effect against H2O2 keratinocyte damage.


Assuntos
Antioxidantes , Alho , Humanos , Antioxidantes/metabolismo , Peróxido de Hidrogênio/toxicidade , Alho/metabolismo , Telúrio/farmacologia , Células HaCaT/metabolismo , Cobalto/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo
7.
Int J Mol Sci ; 23(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36232999

RESUMO

Antibacterial tellurium nanoparticles have the advantages of high activity and biocompatibility. Microbial synthesis of Te nanoparticles is not only a green technology but builds new ecological relationships in diverse environments. However, the antibacterial mechanism of Te nanoparticles is largely unclear. In this study, we report the bacterial synthesis of rod-shaped Te nanoparticles (BioTe) with high antibacterial activity against Escherichia coli. Morphology and permeability examination indicates that membrane damage is the primary reason for the antibacterial activity of BioTe, rather than ROS production and DNA damage. Moreover, a comparison of transcriptome and relative phenotypes reveals the difference in antibacterial mechanisms between BioTe and tellurite. Based on our evidence, we propose an antibacterial mode of rod-shaped BioTe, in which positively charged BioTe interact with the cell membrane through electrostatic attraction and then penetrate the membrane by using their sharp ends. In contrast, tellurite toxicity might be involved in sulfur metabolism.


Assuntos
Nanopartículas , Telúrio , Antibacterianos/farmacologia , Escherichia coli/metabolismo , Espécies Reativas de Oxigênio , Enxofre , Telúrio/metabolismo , Telúrio/farmacologia
8.
Front Public Health ; 10: 946370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091562

RESUMO

Objectives: To establish a MacConkey-potassium tellurium medium-based method for selectively culturing terW gene-positive Klebsiella pneumoniae (KP), to evaluate its performance and apply it to identifying particular clonal hypervirulent KP (hvKP) strains in epidemiological surveillance. Methods: The virulence genes, rmpA, iutA, and terW, were detected by PCR. The minimum inhibitory concentration of potassium tellurite of hvKP (rmpA +/ iutA +) and classical KP (rmpA - and iutA -) was determined using the agar dilution method. The MacConkey medium containing 4 µg/ml potassium tellurite was prepared and the performance in detecting terW + KP was evaluated, including an agreement with PCR and positive/negative predictive value. Fecal samples from healthy volunteers in Fujian were collected and cultured in the medium, then positive strains were identified using MALDI-TOF MS, antimicrobial susceptibility was tested by Kirby-Bauer assays, and virulence genes and capsular serotype genes were tested by PCR. Results: In KP isolated from clinical specimens (N = 198), the positive rate of terW was 37.9%, and the detection rate of terW in hvKP was significantly higher than that in classical KP (70.6% vs 13.3%). The potassium tellurite resistance levels of terW + (N = 75) and terW - (N = 55) KP were 8-128 µg/ml and <1-8 µg/ml, respectively, with significant differences. KP was selectively cultured on a MacConkey medium with 4 µg/ml potassium tellurite, and its agreement with PCR was good (Kappa=0.936), and the positive and negative percent agreement and positive and negative predictive values were 100% (75/75), 92.7% (51/55), 94.9% (75/79), and 100% (51/51), respectively. The prevalence of tellurite-resistant KP was 16.7% (86/516) in fecal samples from healthy volunteers, among which the positive rate of terW was 100% (86/86). The antimicrobial resistance characteristics of terW + KP showed no difference between healthy volunteers and inpatients. The most common capsular serotypes associated with high virulence were K1, K2, and K57. Conclusions: The MacConkey medium containing 4 µg/ml potassium tellurite could easily select and culture terW + KP in fecal samples with high sensitivity and specificity, which is a practical method for the epidemic surveillance of hvKP in the general population.


Assuntos
Anti-Infecciosos , Infecções por Klebsiella , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Telúrio/farmacologia
9.
World J Microbiol Biotechnol ; 38(11): 188, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972591

RESUMO

Selenium (SeNPs) and tellurium nanoparticles (TeNPs) were synthesized by green technology using the three new bacterial marine isolates (strains PL 2476, AF 2469 and G 2451). Isolates were classified as Pseudoalteromonas shioyasakiensis according to 16S rRNA sequence analysis, morphological characteristics, and biochemical reactions. The bioreduction processes of isolates were studied in comparison with the previously described Alteromonas macleodii (strain 2328). All strains exhibited significant tolerance to selenite and tellurite up to 1000 µg/mL. A comparative analysis of the bioreduction processes of the isolates demonstrated that the strains have a high rate of reduction processes. Characterization of biogenic red SeNPs and black TeNPs using scanning electron microscopy (SEM), EDX analysis, Dynamic Light Scattering, and micro-Raman Spectroscopy revealed that all the isolates form stable spherical selenium and tellurium nanoparticles whose size as well as elemental composition depend on the producer strain. Nanoparticles of the smallest size (up to 100 nm) were observed only for strain PL 2476. Biogenic SeNPs and TeNPs were also characterized and tested for their antimicrobial, antifouling and cytotoxic activities. Significant antimicrobial activity was shown for nanoparticles at relatively high concentrations (500 and 1000 µg/mL), with the antimicrobial activity of TeNPs being more significant than SeNPs. In contrast, against cell cultures (breast cancer cells (SkBr3) and human dermal fibroblasts (HDF) SeNPs showed greater toxicity than tellurium nanoparticles. Studies have demonstrated the high antifouling effectiveness of selenium and tellurium nanoparticles when introduced into self-polishing coatings. According to the results obtained, the use of SeNPs and TeNPs as antifouling additives can reduce the concentration of leachable biocides used in coatings, reducing the pressure on the environment.


Assuntos
Nanopartículas , Selênio , Bactérias , Humanos , Nanopartículas/química , RNA Ribossômico 16S/genética , Selênio/farmacologia , Telúrio/química , Telúrio/farmacologia
10.
Drug Resist Updat ; 63: 100844, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35533630

RESUMO

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Selênio , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio , Selênio/química , Selênio/farmacologia , Selênio/uso terapêutico , Telúrio/química , Telúrio/farmacologia , Telúrio/uso terapêutico
11.
J Mater Chem B ; 10(10): 1571-1581, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35147632

RESUMO

The ever-growing antibiotic-resistant bacteria pose a huge threat to public health. Restoring the susceptibility of ineffective antibiotics by inorganic nanomaterials and combining the photothermal and antibiotic effects could be an optional strategy to combat this resistance. Here, cefotaxime (CTX) loaded tellurium nanoparticles (Te NPs) were fabricated to recover the antibacterial activity of the ineffective ß-lactam antibiotic CTX against methicillin-resistant Staphylococcus aureus (MRSA) and at the same time perform photothermal therapy under light-emitting diode (LED) irradiation with a wavelength in the range of 420-480 nm. The combination of 50 µg mL-1 Te-CTX NPs with 5 min LED irradiation produced a 30.4 °C temperature increase and killed 99% of MRSA in vitro. In vivo evaluation in mice revealed that Te-CTX NPs and LED irradiation accelerated the healing of MRSA infected wounds and presented biosafety. Furthermore, this combination accelerated glutathione oxidation and resulted in the disruption of the antioxidant defence system of MRSA. Such a synergistic antibiotic and photothermal therapy provides an innovative way for the treatment of antibiotic-resistant bacterial infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefotaxima , Sinergismo Farmacológico , Camundongos , Telúrio/farmacologia
12.
Anal Chem ; 94(8): 3608-3616, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35179864

RESUMO

The hepatotoxicity of cadmium-based quantum dots (Cd-QDs) has become the focus with their extensive applications in biomedicine. Previous reports have demonstrated that high oxidative stress and consequent redox imbalance play critical roles in their toxicity mechanisms. Intracellular antioxidant proteins, such as thioredoxin 1 (Trx1) and peroxiredoxin 1 (Prx1), could regulate redox homeostasis through thiol-disulfide exchange. Herein, we hypothesized that the excessive reactive oxygen species (ROS) induced by Cd-QD exposure affects the functions of Trx1 or Prx1, which further causes abnormal apoptosis of liver cells and hepatotoxicity. Thereby, three types of Cd-QDs, CdS, CdSe, and CdTe QDs, were selected for conducting an intensive study. Under the same conditions, the H2O2 level in the CdTe QD group was much higher than that of CdS or CdSe QDs, and it also corresponded to the higher hepatotoxicity. Mass spectrometry (MS) results show that excessive H2O2 leads to sulfonation modification (-SO3H) at the active sites of Trx1 (Cys32 and Cys35) and Prx1 (Cys52 and Cys173). The irreversible oxidative modifications broke their cross-linking with the apoptosis signal-regulating kinase 1 (ASK1), resulting in the release and activation of ASK1, and activation of the downstream JNK/p38 signaling finally promoted liver cell apoptosis. These results highlight the key effect of the high oxidative stress, which caused irreversible oxidative modifications of Trx1 and Prx1 in the mechanisms involved in Cd-QD-induced hepatotoxicity. This work provides a new perspective on the hepatotoxicity mechanisms of Cd-QDs and helps design safe and reliable Cd-containing nanoplatforms.


Assuntos
Compostos de Cádmio , Doença Hepática Induzida por Substâncias e Drogas , Pontos Quânticos , Cádmio/toxicidade , Compostos de Cádmio/toxicidade , Humanos , Peróxido de Hidrogênio/farmacologia , Oxirredução , Estresse Oxidativo , Peroxirredoxinas/metabolismo , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Telúrio/farmacologia , Tiorredoxinas/metabolismo
13.
Acta Parasitol ; 67(1): 143-152, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34173967

RESUMO

PURPOSE: Today, the use of natural products and nanostructures has increased. Given the reports on beneficial effects of various organotellurane compounds on types of visceral leishmaniasis, we decided to investigate the effect of TeO2 NPs on Leishmania major (L. major). Tellurium can cause cell apoptosis in cancer cells without activating the caspase-pathway. METHODS: TeO2 NPs at first synthesized and the structure was checked by XRD, SEM and EDS tests. The cytotoxic effect of TeO2 NPs against L. major promastigotes, amastigotes and macrophages was assessed by MTT test or counting. The possible apoptosis of L. major by TeO2 NPs was evaluated by flow cytometry test. For in vivo assay, the lesions of infected BALB/c mice with L. major promastigotes were treated with TeO2 NPs, then the lesion size and survival rate were evaluated. RESULTS: The synthesis of TeO2 with tetragonal structure was confirmed by XRD. The combination of nanorods and nanoflakes and the presence of Te were proven by SEM and EDS, respectively. According the effects of nanoparticle on promastigotes and amastigotes, the IC50 values of TeO2 after 72 h of incubation were 15.13 and 52.22 µg/ml, respectively. TeO2 NPs induced apoptosis in about 41% of promastigotes. The ulcer greatly healed and survival rate was higher in treated mice compared to those in control group. CONCLUSION: Based on the data, favorable anti-leishmanial properties were observed by using TeO2 NPs. TeO2 NPs have cytotoxic impacts on L. major promastigotes and amastigotes in vitro and in vivo and may be regarded as a therapy option.


Assuntos
Antiprotozoários , Leishmania major , Nanotubos , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Óxidos/farmacologia , Telúrio/farmacologia
14.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638861

RESUMO

Among organic-inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), using a cell culture system. DPDTe exhibited strong cytotoxicity against vascular endothelial cells and fibroblasts along with high intracellular accumulation but showed no cytotoxicity and had less accumulation in vascular smooth muscle cells and renal epithelial cells. The cytotoxicity of DPDTe decreased when intramolecular tellurium atoms were replaced with selenium or sulfur atoms. Electronic state analysis revealed that the electron density between tellurium atoms in DPDTe was much lower than those between selenium atoms of diphenyl diselenide and sulfur atoms of diphenyl disulfide. Moreover, diphenyl telluride did not accumulate and exhibit cytotoxicity. The cytotoxicity of DPDTe was also affected by substitution. p-Dimethoxy-DPDTe showed higher cytotoxicity, but p-dichloro-DPDTe and p-methyl-DPDTe showed lower cytotoxicity than that of DPDTe. The subcellular distribution of the compounds revealed that the compounds with stronger cytotoxicity showed higher accumulation rates in the mitochondria. Our findings suggest that the electronic state of tellurium atoms in DPDTe play an important role in accumulation and distribution of DPDTe in cultured cells. The present study supports the hypothesis that nucleophilic organometallic compounds, as well as electrophilic organometallic compounds, exhibit cytotoxicity by particular mechanisms.


Assuntos
Derivados de Benzeno/farmacologia , Células Endoteliais/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Compostos Organosselênicos/farmacologia , Telúrio/farmacologia , Animais , Derivados de Benzeno/química , Derivados de Benzeno/metabolismo , Bovinos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Células LLC-PK1 , Modelos Químicos , Estrutura Molecular , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Compostos Organosselênicos/química , Compostos Organosselênicos/metabolismo , Suínos , Telúrio/química
15.
Biometals ; 34(4): 937-946, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34255250

RESUMO

The tellurium oxyanion tellurate is toxic to living organisms even at low concentrations; however, its mechanism of toxicity is poorly understood. Here, we show that exposure of Escherichia coli K-12 to tellurate results in reduction to elemental tellurium (Te[0]) and the formation of intracellular reactive oxygen species (ROS). Toxicity assays performed with E. coli indicated that pre-oxidation of the intracellular thiol pools increases cellular resistance to tellurate-suggesting that intracellular thiols are important in tellurate toxicity. X-ray absorption spectroscopy experiments demonstrated that cysteine reduces tellurate to elemental tellurium. This redox reaction was found to generate superoxide anions. These results indicate that tellurate reduction to Te(0) by cysteine is a source of ROS in the cytoplasm of tellurate-exposed cells.


Assuntos
Cisteína/metabolismo , Escherichia coli K12/efeitos dos fármacos , Telúrio/farmacologia , Escherichia coli K12/citologia , Escherichia coli K12/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Telúrio/metabolismo
16.
Int J Biol Macromol ; 184: 990-999, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197852

RESUMO

To explore in vivo application of quantum dots (QDs), it is essential to understand the dynamics and energetics of interactions between QDs and proteins. Here, surface plasmon resonance (SPR) and molecular docking were employed to investigate the kinetics and thermodynamics of interactions between human serum albumin (HSA) and CdTe QDs (~3 nm) functionalized with mercaptopropionic acid (MPA) or thioglycolic acid (TGA). Kinetic analysis showed that HSA-QD interactions involved transition-complex formation. Despite the structural similarities between MPA and TGA, the [HSA-CdTe@TGA]‡ formation by association of free HSA and QDs demanded 70% more energy and higher entropic gain (Ea-TGA‡= 65.10 and T∆Sa-TGA‡= 28.62 kJ mol-1) than the formation of [HSA-CdTe@MPA]‡ (Ea-MPA‡ = 38.13 and T∆Sa-MPA‡ = 0.53kJ mol-1). While the [HSA-CdTe@MPA]° dissociation required higher energy and lower entropy loss (Ed-MPA‡ = 49.96 and T∆Sd-MPA‡ = - 32.18kJ mol-1) than the [HSA-CdTe@TGA]° dissociation (Ed-TGA‡= 30.78 and T∆Sd-TGA‡= - 51.12 kJ mol-1). The stability of [HSA-QDs]° was independent of the temperature and functionalizing group. However, the enthalpic and entropic components were highly affected by the substitution of MPA (ΔH° = - 11.83 and TΔS° = 32.72 kJ mol-1) with TGA (ΔH° = 34.31 and TΔS° = 79.73 kJ mol-1). Furthermore, molecular docking results indicated that the metal site on the QDs contributes to the stabilization of [HSA-QDs]°. Therefore, differences in QD functionalization and surface coverage densities can alter the HSA-QD interaction, thus their application.


Assuntos
Compostos de Cádmio/farmacologia , Albumina Sérica Humana/metabolismo , Compostos de Sulfidrila/química , Telúrio/farmacologia , Tioglicolatos/química , Compostos de Cádmio/química , Entropia , Humanos , Cinética , Simulação de Acoplamento Molecular , Pontos Quânticos , Albumina Sérica Humana/química , Ressonância de Plasmônio de Superfície , Telúrio/química , Termodinâmica
17.
Biometals ; 34(5): 1007-1016, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34173930

RESUMO

Pseudomonas aeruginosa, an opportunistic human pathogen, is a major health concern as it grows as a biofilm and evades the host's immune defenses. Formation of biofilms on catheter and endotracheal tubes demands the development of biofilm-preventive (anti-biofilm) approaches and evaluation of nanomaterials as alternatives to antibiotics. The present study reports the successful biosynthesis of tellurium nanorods using cell lysate of Haloferax alexandrinus GUSF-1 (KF796625). The black particulate matter had absorption bands at 0.5 and 3.6 keV suggestive of elemental tellurium; showed x-ray diffraction peaks at 2θ values 24.50°, 28.74°, 38.99°, 43.13°, 50.23° and displayed a crystallite size of 36.99 nm. The black nanorods of tellurium were an average size of 40 nm × 7 nm, as observed in transmission electron microscopy. To our knowledge, the use of cell lysate of Haloferax alexandrinus GUSF-1 (KF796625) as a green route for the biosynthesis of tellurium nanorods with a Pseudomonas aeruginosa biofilm inhibiting capacity is novel to haloarchaea. At 50 µg mL-1, these tellurium nanorods exhibited 75.03% in-vitro reduction of biofilms of Pseudomonas aeruginosa ATCC 9027, comparable to that of ciprofloxacin, which is used in treatment of Pseudomonas infections. Further, the observed ability of these nanoparticles to inhibit the formation of Pseudomonas biofilms is worthy of future research perusal.


Assuntos
Haloferax , Nanotubos , Infecções por Pseudomonas , Antibacterianos/farmacologia , Biofilmes , Humanos , Pseudomonas aeruginosa , Telúrio/farmacologia
18.
J Mater Chem B ; 9(35): 7271-7277, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34121105

RESUMO

Photothermal therapy (PTT) stimulated by light in the second near-infrared (NIR-II) biowindow shows great superiorities in the penetration ability of tissue and maximum permissible exposure (MPE). Exploring new photothermal agents with good optical absorbance in the NIR-II region is highly desirable for efficient cancer therapy. Herein, we successfully prepare carambola-like bismuth telluride (Bi2Te3) superstructures modified with PEGylated phospholipid (Bi2Te3@PEG) for CT imaging-guided PTT in the NIR-II biowindow. Attributing to their superstructures, Bi2Te3@PEG exhibited enhanced photoabsorption with higher photothermal conversion efficiency (55.3% for 1064 nm) compared with that of Bi2Te3 nanoparticles. Furthermore, the good X-ray attenuation capacity of Bi endows Bi2Te3@PEG with an outstanding performance as computed tomography (CT) contrast agents. Bi2Te3@PEG superstructures have been confirmed to effectively eliminate tumor in vitro and in vivo with negligible long-term toxicities, offering them great potential to act as theranostic platforms for cancer diagnosis and treatment.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Bismuto/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Telúrio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Bismuto/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Raios Infravermelhos , Teste de Materiais , Camundongos , Camundongos Endogâmicos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Telúrio/química , Tomografia Computadorizada por Raios X
19.
Bioorg Med Chem Lett ; 45: 128147, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052322

RESUMO

We evaluated in vitro a series of telluride containing compounds bearing the benzenesulfonamide group, as effective inhibitors of the physiologically relevant human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) enzymes I, II, IV VII and IX. The potent effects of such compounds against the tumor-associated hCA IX being low nanomolar inhibitors (KI 2.2 to 2.9 nM) and with good selectivity over the ubiquitous hCA II, gave the possibility to evaluate their lethal effect in vitro against a breast cancer cell line (MDA-MB-231). Among the series, both compounds 3a and 3g induced significant toxic effects against tumor cells after 48 h incubation. Under normoxic condition 3a showed high efficacy killing over 94% of tumor cells at 1 µM, and derivative 3g reached the tumor cell viability under the 5% at 10 µM. In hypoxic condition, these two compounds showed less effective although retained excellent cancer cell killer. These unusual features make them interesting lead compounds acting as antitumor agents also in tumor types not dependent from hCA IX overexpression.


Assuntos
Antineoplásicos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Sulfonamidas/farmacologia , Telúrio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Telúrio/química
20.
ACS Appl Mater Interfaces ; 13(13): 14885-14893, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33754695

RESUMO

The surge of antibiotic-resistant bacteria is leading to the loss of effectiveness of antibiotic treatment, resulting in prolonged infections and even death. Against this healthcare threat, antimicrobial nanoparticles that hamper the evolution of resistance mechanisms are promising alternatives to antibiotics. Herein, we used Kraft lignin, a poorly valorized polymer derived from plant biomass, to develop novel hybrid tellurium-lignin nanoparticles (TeLigNPs) as alternative antimicrobial agents. The sonochemically synthesized TeLigNPs are comprised of a lignin matrix with embedded Te clusters, revealing the role of lignin as both a reducing agent and a structural component. The hybrid NPs showed strong bactericidal effects against the Gram-negative Escherichia coli and Pseudomonas aeruginosa, achieving more than 5 log bacteria reduction, while they only slightly inhibited the growth of the Gram-positive Staphylococcus aureus. Exposure of TeLigNPs to human cells did not cause morphological changes or reduction in cell viability. Studies on the antimicrobial mechanism of action demonstrated that the novel TeLigNPs were able to disturb bacterial model membranes and generate reactive oxygen species (ROS) in Gram-negative bacteria.


Assuntos
Antibacterianos/farmacologia , Lignina/farmacologia , Nanopartículas , Telúrio/farmacologia , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Lignina/química , Nanopartículas/química , Nanopartículas/ultraestrutura , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Telúrio/química
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