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1.
Sci Rep ; 14(1): 7663, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561404

RESUMO

Heavy metal contamination is an urgent ecological governance problem in mining areas. In order to seek for a green and environmentally friendly reagent with better plant restoration effect to solve the problem of low efficiency in plant restoration in heavy metal pollution soil. In this study, we evaluated the effects of three biodegradable chelating agents, namely citric acid (CA), fulvic acid (FA) and polyaspartic acid (PASP), on the physicochemical properties of copper tailings, growth of ryegrass (Lolium perenne L.) and heavy metal accumulation therein. The results showed that the chelating agent application improved the physicochemical properties of copper tailings, increased the biomass of ryegrass and enriched more Cu and Cd in copper tailings. In the control group, the main existing forms of Cu and Cd were oxidizable state, followed by residual, weak acid soluble and reducible states. After the CA, FA or PASP application, Cu and Cd were converted from the residual and oxidizable states to the reducible and weak acid soluble states, whose bioavailability in copper tailings were thus enhanced. Besides, the chelating agent incorporation improved the Cu and Cd extraction efficiencies of ryegrass from copper tailings, as manifested by increased root and stem contents of Cu and Cd by 30.29-103.42%, 11.43-74.29%, 2.98-110.98% and 11.11-111.11%, respectively, in comparison with the control group. In the presence of multiple heavy metals, CA, FA or PASP showed selectivity regarding the ryegrass extraction of heavy metals from copper tailings. PCA analysis revealed that the CA-4 and PASP-7 treatment had great remediation potentials against Cu and Cd in copper tailings, respectively, as manifested by increases in Cu and Cd contents in ryegrass by 90.98% and 74.29% compared to the CK group.


Assuntos
Lolium , Metais Pesados , Poluentes do Solo , Cobre/metabolismo , Cádmio/metabolismo , Quelantes/farmacologia , Biodegradação Ambiental , Poluentes do Solo/metabolismo , Metais Pesados/análise , Ácidos/metabolismo , Solo/química
2.
Inorg Chem ; 63(16): 7520-7539, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38590210

RESUMO

A new set of binuclear arene ruthenium complexes [Ru2(p-cymene)2(k4-N2OS)(L1-L3)Cl2] (Ru2L1-Ru2L3) encompassing furan-2-carboxamide-based aroylthiourea derivatives (H2L1-H2L3) was synthesized and characterized by various spectral and analytical techniques. Single-crystal XRD analysis unveils the N^O and N^S mixed monobasic bidentate coordination of the ligands constructing N, S, Cl/N, O, and Cl legged piano stool octahedral geometry. DFT analysis demonstrates the predilection for the formation of stable arene ruthenium complexes. In vitro antiproliferative activity of the complexes was examined against human cervical (HeLa), breast (MCF-7), and lung (A549) cancerous and noncancerous monkey kidney epithelial (Vero) cells. All the complexes are more efficacious against HeLa and MCF-7 cells with low inhibitory doses (3.86-11.02 µM). Specifically, Ru2L3 incorporating p-cymene and -OCH3 fragments exhibits high lipophilicity, significant cytotoxicity against cancer cells, and lower toxicity on noncancerous cells. Staining analysis indicates the apoptosis-associated cell morphological changes expressively in MCF-7 cells. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) analyses reveal that Ru2L3 can raise ROS levels, reduce MMP, and trigger mitochondrial dysfunction-mediated apoptosis. The catalytic oxidation of glutathione (GSH) to its disulfide form (GSSG) by the complexes may simultaneously increase the ROS levels, alluding to their observed cytotoxicity and apoptosis induction. Flow cytometry determined the quantitative classification of late apoptosis and S-phase arrest in MCF-7 and HeLa cells. Western blotting analysis confirmed that the complexes promote apoptosis by upregulating Caspase-3 and Caspase-9 and downregulating BCL-2. Molecular docking studies unfolded the strong binding affinities of the complexes with VEGFR2, an angiogenic signaling receptor, and BCL2, Cyclin D1, and HER2 proteins typically overexpressed on tumor cells.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Complexos de Coordenação , Ensaios de Seleção de Medicamentos Antitumorais , Rutênio , Tioureia , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Rutênio/química , Rutênio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Tioureia/química , Tioureia/farmacologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Animais , Estrutura Molecular , Furanos/química , Furanos/farmacologia , Furanos/síntese química , Quelantes/química , Quelantes/farmacologia , Quelantes/síntese química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Chlorocebus aethiops , Espécies Reativas de Oxigênio/metabolismo , Células Vero , Relação Estrutura-Atividade
3.
Inorg Chem ; 63(16): 7464-7472, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38598182

RESUMO

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.


Assuntos
Cinamatos , Urânio , Cinamatos/química , Cinamatos/farmacologia , Animais , Ligantes , Camundongos , Urânio/química , Urânio/metabolismo , Urânio/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Linhagem Celular , Teoria da Densidade Funcional , Ratos , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Quelantes/farmacologia , Quelantes/síntese química
4.
Huan Jing Ke Xue ; 45(3): 1803-1811, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471891

RESUMO

To investigate the effect of chelating agents on plant uptake of heavy metals, castor (Ricinus communis L.) was used as the test plant. Soil culture and pot experiments were conducted to study the effects of different concentrations of ethylenediamine disuccinic acid (EDDS) on the forms of Cu and Cd in soil and their absorption and transport by castor. The results showed that the application of EDDS significantly increased the content of available Cu and Cd. After 15 days of cultivation, the available Cu and Cd concentrations in the soil increased by 43.01%-103.55% and 51.78%-69.43%, respectively. EDDS promoted the conversion of reducible Cu to weak acid extractable and increased the mobility of Cu. Meanwhile, the application of EDDS promoted the absorption, transport, and enrichment of Cu in castor. Under the application of 2.5 mmol·kg-1 EDDS and 5.0 mmol·kg-1 EDDS, the Cu concentrations in the shoots were 4.88 times and 16.65 times higher than that of the control (P< 0.05), and the Cu concentrations in the roots were 2.89 times and 3.60 times higher than that of the control (P< 0.05), respectively. The Cu transport coefficient significantly increased by 72.73% and 381.82% when treated with EDDS 2.5 and EDDS 5.0. Simultaneously, the phytoextraction of Cu in shoots, roots, and their sum were 14.08, 2.16, and 4.70 times higher than that of the control (P<0.05), respectively, when treated with EDDS 5.0. Furthermore, EDDS significantly increased the Cd concentrations in castor. When treated with EDDS 2.5 the shoots and roots increased by 15.15% and 57.42%, respectively, and the phytoextraction of total Cd significantly increased by 13.44%. Generally, the EDDS treatment could increase the available Cu and Cd in soil, promote the uptake of Cu and Cd, and improve the phytoremediation efficiency of castor. Among them, the addition of 5.0 mmol·kg-1 EDDS had the best effect for Cu, whereas the addition of 2.5 mmol kg-1 EDDS had a higher increase in the phytoextraction of Cd.


Assuntos
Metais Pesados , Poluentes do Solo , Cádmio/análise , Solo , Poluentes do Solo/análise , Metais Pesados/análise , Etilenodiaminas , Quelantes/farmacologia , Biodegradação Ambiental , Succinatos/farmacologia
5.
Microbiol Spectr ; 12(4): e0409523, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38376363

RESUMO

Candida albicans, one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against C. albicans is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug's target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a C. albicans clinical isolate and identified 17 molecules that inhibited C. albicans growth by >80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans Candida, including Candida auris and Candida glabrata, with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould Aspergillus fumigatus. Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued C. albicans growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen C. albicansIMPORTANCEThe worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen Candida albicans is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against C. albicans. Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including Candida auris and Aspergillus fumigatus. Finally, we determined that these compounds inhibit the growth of C. albicans in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.


Assuntos
Produtos Biológicos , Micoses , Xantonas , Humanos , Candida albicans , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Farmacorresistência Fúngica , Quelantes/farmacologia , Quelantes/uso terapêutico , Aspergillus fumigatus , Ferro , Xantonas/uso terapêutico , Testes de Sensibilidade Microbiana
6.
Redox Biol ; 70: 103076, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340635

RESUMO

Wilson's disease (WD) is a genetic disorder that primarily leads to the pathological accumulation of copper (Cu) in the liver, causing an abnormal increase in reactive oxygen species (ROS). The prevailing clinical therapy for WD involves lifelong use of Cu chelation drugs to facilitate Cu excretion in patients. However, most available drugs exert severely side-effects due to their non-specific excretion of Cu, unsuitable for long-term use. In this study, we construct a prochelator that enables precise and controlled delivery of Cu chelator drugs to the liver in WD model, circumventing toxic side effects on other organs and normal tissues. This innovative prochelator rapidly releases the chelator and the fluorescent molecule methylene blue (MB) upon activation by ROS highly expressed in the liver of WD. The released chelator coordinates with Cu, efficiently aiding in Cu removal from the body and effectively inhibiting the pathological progression of WD.


Assuntos
Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/patologia , Quelantes/farmacologia , Quelantes/uso terapêutico , Espécies Reativas de Oxigênio , Cobre
7.
Ecotoxicol Environ Saf ; 272: 116113, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364761

RESUMO

Heavy metals in soil significantly threaten human health, and their remediation is essential. Among the various techniques used, phytoremediation is one of the safest, most innovative, and effective. In recent years, the use of biodegradable chelators to assist plants in improving their remediation efficiency has gained popularity. These biodegradable chelators aid in the transformation of metal ions or metalloids, thereby facilitating their mobilization and uptake by plants. Developed countries are increasingly adopting biodegradable chelators for phytoremediation, with a growing emphasis on green manufacturing and technological innovation in the chelating agent market. Therefore, it is crucial to gain a comprehensive understanding of the mechanisms and market prospects of biodegradable chelators for phytoremediation. This review focuses on elucidating the uptake, translocation, and detoxification mechanisms of chelators in plants. In this study, we focused on the effects of biodegradable chelators on the growth and environmental development of plants treated with phytoremediation agents. Finally, the potential risks associated with biodegradable chelator-assisted phytoremediation are presented in terms of their availability and application prospects in the market. This study provides a valuable reference for future research in this field.


Assuntos
Metais Pesados , Poluentes do Solo , Humanos , Biodegradação Ambiental , Quelantes/farmacologia , Estudos de Viabilidade , Poluentes do Solo/análise , Plantas/metabolismo , Metais Pesados/análise , Solo
8.
Dalton Trans ; 53(11): 5089-5104, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38375922

RESUMO

Au(III) bis(pyrrolide-imine) chelates are emerging as a class of versatile, efficacious metallodrug candidates. Here, we synthesised two enantiopure chiral ligands H2L1 and H2L2 (tetradentate cyclohexane-1,2-diamine-bridged bis(pyrrole-imine) derivatives). Metallation of the ligands with Au(III) afforded the chiral cationic complexes AuL1 and AuL2. The in vitro cytotoxicities of AuL1 and AuL2 determined in the NCI-60 single-dose drug screen were 56.5% and 89.1%, respectively. AuL1 was subsequently selected for a five-dose NCI-60 screen, attaining GI50, IC50, and LC50 values of 4.7, 9.3 and 39.8 µM, respectively. Hierarchical cluster analysis of the NCI-60 data indicated that the profile for AuL1 was similar to that of vinblastine sulfate, a microtubule-targeting vinca alkaloid. Reactions of AuL1 with glutathione (GSH) in vitro confirmed its susceptibility to reduction, Au(III) → Au(I), by intracellular thiols. Because human serum albumin (HSA) is responsible for transporting clinically deployed and investigational drugs, we studied the uptake of AuL1 and AuL2 by HSA to delineate how chirality impacts their protein-binding affinity. Steady-state fluorescence quenching data acquired on the native protein and data from site-specific probes showed that the compounds bind at sites close enough to Trp-214 (subdomain IIA) of HSA to quench the fluorophore. The bimolecular quenching rate constants, Kq, were ca. 102 times higher than the maximum diffusion-controlled collision constant of a biomolecule in water (1010 M-1 s-1), confirming that static fluorescence quenching was the dominant mechanism. The Stern-Volmer constants, KSV, were ∼104 M-1 at 37 °C, while the affinity constants, Ka (37 °C), measured ∼2.1 × 104 M-1 (AuL1) and ∼1.2 × 104 M-1 (AuL2) for enthalpy-driven ligand uptake targeting Sudlow's site I. Although far- and near-UV CD spectroscopy indicated that both complexes minimally perturb the secondary and tertiary structure of HSA, substantial shifts in the CD spectra were recorded for both protein-bound ligands. This study highlights the role of chirality in determining the cytotoxicity profiles and protein binding behaviour of enantiomeric Au(III) chelates.


Assuntos
Quelantes , Albumina Sérica Humana , Humanos , Albumina Sérica Humana/química , Sítios de Ligação , Ligação Proteica , Análise Espectral , Quelantes/farmacologia , Iminas , Espectrometria de Fluorescência , Termodinâmica , Dicroísmo Circular , Simulação de Acoplamento Molecular
9.
Arch Pharm (Weinheim) ; 357(4): e2300648, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279543

RESUMO

Metalloenzymes play vital roles in various biological processes, requiring the search for inhibitors to develop treatment options for diverse diseases. While compound library screening is a conventional approach, the exploration of virtual chemical spaces housing trillions of compounds has emerged as an alternative strategy. In this study, we investigated the suitability of selected screening libraries and chemical spaces for discovering inhibitors of metalloenzymes featuring common ions (Mg2+, Mn2+, and Zn2+). First, metal-coordinating groups from ligands interacting with ions in the Protein Data Bank were extracted. Subsequently, the prevalence of these groups in two focused screening libraries (Life Chemicals' chelator library, comprising 6,428 compounds, and Otava's chelator fragment library, with 1,784 fragments) as well as two chemical spaces (GalaXi and REAL space, containing billions of virtual products) was investigated. In total, 1,223 metal-coordinating groups were identified, with about a quarter of these groups found within the examined libraries and spaces. Our results indicate that these can serve as valuable starting points for drug discovery targeting metalloenzymes. In addition, this study suggests ways to improve libraries and spaces for better success in finding potential inhibitors for metalloenzymes.


Assuntos
Metaloproteínas , Relação Estrutura-Atividade , Metaloproteínas/química , Metaloproteínas/metabolismo , Descoberta de Drogas , Metais , Quelantes/farmacologia , Íons
10.
Compr Rev Food Sci Food Saf ; 23(1): e13277, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284607

RESUMO

In the past decade, food-derived metal-chelating peptides (MCPs) have attracted significant attention from researchers working towards the prevention of metal (viz., iron, zinc, and calcium) deficiency phenomenon by primarily inhibiting the precipitation of metals caused by the gastrointestinal environment and exogenous substances (including phytic and oxalic acids). However, for the improvement of limits of current knowledge foundations and future investigation directions of MCP or their derivatives, several review categories should be improved and emphasized. The species' uniqueness and differences in MCP productions highly contribute to the different values of chelating ability with particular metal ions, whereas comprehensive reviews of chelation characterization determined by various kinds of technique support different horizons for explaining the chelation and offer options for the selection of characterization methods. The reviews of chelation mechanism clearly demonstrate the involvement of potential groups and atoms in chelating metal ions. The discussions of digestive stability and absorption in various kinds of absorption model in vitro and in vivo as well as the theory of involved cellular absorption channels and pathways are systematically reviewed and highlighted compared with previous reports as well. Meanwhile, the chelation mechanism on the molecular docking level, the binding mechanism in amino acid identification level, the utilizations of everted rat gut sac model for absorption, and the involvement of cellular absorption channels and pathway are strongly recommended as novelty in this review. This review makes a novel contribution to the literature by the comprehensive prospects for the research and development of food-derived mineral supplements.


Assuntos
Quelantes , Metais , Ratos , Animais , Simulação de Acoplamento Molecular , Quelantes/química , Quelantes/metabolismo , Quelantes/farmacologia , Metais/química , Peptídeos/química , Íons , Digestão
11.
PLoS One ; 19(1): e0296647, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38232127

RESUMO

This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (p<0.001). In Retro MTA group, samples treated with DR HEDP and 17% EDTA had higher dislodgment resistance compared to 7% MA (p<0.001). On microstructural and elemental analysis of all the three MTA cements, samples treated with 17% EDTA and 7% MA were more amorphous and granular when compared to DR HEDP, which was pettle shaped. Calcium level was decreased more in samples treated with 17% EDTA and 7% MA when compared to DR HEDP.


Assuntos
Quelantes , Ácido Etidrônico , Maleatos , Quelantes/farmacologia , Ácido Edético/farmacologia , Compostos de Cálcio/farmacologia , Compostos de Cálcio/química , Silicatos/farmacologia , Silicatos/química , Combinação de Medicamentos , Óxidos/farmacologia , Óxidos/química
12.
Dalton Trans ; 53(5): 1977-1988, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38205595

RESUMO

Most platinum group-based cyclometalated neutral and cationic anticancer complexes with the general formula [(C^N)2Ir(XY)]0/+ (neutral complex: XY = bidentate anionic ligand; cationic complex: XY = bidentate neutral ligand) are notable owing to their intrinsic luminescence properties, good cell permeability, interaction with some biomolecular targets and unique mechanisms of action (MoAs). We herein synthesized a series of neutral and cationic amine-imine cyclometalated iridium(III) complexes using Schiff base ligands with sp2-N/sp3-N N^NH2 chelating donors. The cyclometalated iridium(III) complexes were identified by various techniques. They were stable in aqueous media, displayed moderate fluorescence and exhibited affinity toward bovine serum albumin (BSA). The complexes demonstrated promising cytotoxicity against lung cancer A549 cells, cisplatin-resistant lung cancer A549/DDP cells, cervical carcinoma HeLa cells and human liver carcinoma HepG2 cells, with IC50 values ranging from 9.98 to 19.63 µM. Unfortunately, these complexes had a low selectivity (selectivity index: 1.62-1.98) towards A549 cells and BEAS-2B normal cells. The charge pattern of the metal center (neutral or cationic) and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The study revealed that these complexes could target mitochondria, cause depolarization of the mitochondrial membrane, and trigger the production of intracellular ROS. Additionally, the complexes were observed to induce late apoptosis and perturb the cell cycle in the G2/M or S phase in A549 cells. Based on these results, it appears that the anticancer efficacy of these complexes was predominantly attributed to the redox mechanism.


Assuntos
Antineoplásicos , Carcinoma , Complexos de Coordenação , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Células HeLa , Irídio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/metabolismo , Ligantes , Quelantes/farmacologia , Mitocôndrias/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma/metabolismo , Apoptose , Linhagem Celular Tumoral
13.
Bioorg Med Chem ; 97: 117538, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056379

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative condition with complex pathophysiology. Aggregated amyloid beta (Aß) peptide plaques and higher concentrations of bio-metals such as copper (Cu), zinc (Zn), and iron (Fe) are the most significant hallmarks of AD observed in the brains of AD patients. Therefore simultaneous inhibition of Aß peptide aggregation and reduction of metal stress may serve as an effective therapeutic approach for treating Alzheimer's disease. A series of bifunctional dipeptides bearing squaramide backbone were synthesized and investigated for their ability to chelate metal ions and prevent Aß peptide aggregation. Dipeptides with Valine (V) and Threonine (T) substitutions at the C-terminus exhibited preferential chelation with Cu(II), Zn(II), and Fe(III) metal ions in the presence of other metal ions. They were also found to inhibit the aggregation of Aß peptide in-vitro. A further molecular dynamics (MD) simulation study demonstrated that these two dipeptides interact with the Aß peptide in the hydrophobic core (KLVFF) region. Circular dichroism (CD) study revealed slight conformational change in the Aß peptide upon the interactions with dipeptides. Apart from metal chelation and inhibition of Aß peptide aggregation, the selected dipeptides were found to possess anti-oxidant properties. Therefore, the squaramide backbone-modified dipeptides may serve as an active bifunctional scaffold towards the development of new chemical entities for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/química , Doença de Alzheimer/tratamento farmacológico , Dipeptídeos/farmacologia , Compostos Férricos , Metais , Cobre/farmacologia , Cobre/química , Quelantes/farmacologia , Quelantes/química , Íons , Amiloide
14.
Eur Endod J ; 9(1): 81-88, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37965676

RESUMO

OBJECTIVE: The aim of this in vitro study was to compare the smear layer and debris removal and antimicrobial activity of two dual-action irrigating solutions for continuous chelation (Triton; Brasseler, Savannah, USA and Dual Rinse HEDP; Medcem GmbH, Weinfelden, Switzerland) with a dual step irrigation protocol with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA). METHODS: Thirty single-rooted single-canal teeth were divided into three groups (n=10) and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA. The teeth were observed under a scanning electron microscope (SEM) to assess the canal wall cleanliness. In addition, 80 dentine discs were contaminated with Candida albicans and 80 discs with Enterococcus faecalis and irrigated with Triton, Dual Rinse HEDP mixed with 6% NaOCl and 6% NaOCl/17% EDTA or not treated (n=20). Fifteen discs were used to evaluate colony-forming units, while 5 discs were analysed by SEM. Data were analysed using the Shapiro- Wilk, Kruskal-Wallis and One-Way ANOVA tests. RESULTS: Triton was statistically more effective than Dual Rinse HEDP and NaOCl/EDTA in removing debris (p<0.05), except with NaOCl/EDTA in the coronal third. Triton was more effective than Dual Rinse HEDP in removing the smear layer from the apical and middle thirds (p<0.05). All the irrigation protocols significantly re- duced the number of E. faecalis. The Triton group showed the lowest number of remaining C. albicans (p<0.05). CONCLUSION: Triton was the most effective irrigation solution in removing debris and as effective as NaOCl/ EDTA in removing the smear layer. Triton showed the highest efficacy against C. albicans. New irrigating solutions that provide continuous chelation may provide an alternative to current irrigation protocols.


Assuntos
Anti-Infecciosos , Camada de Esfregaço , Humanos , Ácido Edético/farmacologia , Ácido Etidrônico , Microscopia Eletrônica de Varredura , Cavidade Pulpar , Preparo de Canal Radicular/métodos , Irrigantes do Canal Radicular/farmacologia , Quelantes/farmacologia , Anti-Infecciosos/farmacologia
15.
Odontology ; 112(1): 1-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37433927

RESUMO

This scoping review aimed to synthesize and explore the current boundaries and limitations of laboratory research on the effectiveness of continuous chelation irrigation protocol in endodontics. This scoping review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. Literature search was conducted on Pubmed and Scopus to identify all laboratory studies evaluating smear layer and hard-tissue debris removal or, antimicrobial efficacy, or dentine erosion induced by continuous chelation. Two independent reviewers performed the all review steps and the relevant items were recorded. Seventy-seven potentially relevant studies were identified. Finally, 23 laboratory studies met the eligibility criteria for qualitative synthesis. Seven studies focused on the smear layer/debris removal outcome, 10 on antimicrobial activity, and 10 on dentine erosion. In general, the continuous chelation protocol was equally or more effective in the cleanliness of root canals and antimicrobial activity compared with traditional sequential protocol. In addition, etidronate solutions seemed to be milder chelating agents compared to those with EDTA, thus resulting in reduced or no dentine erosion and roughness modification. Yet, the methodological differences among the included studies limit the results' generalizability. The continuous chelation seems to be equally or more effective in all investigated outcomes when compared with the traditional sequential protocol. The methodological variability among the studies and shortcomings in the methods employed limit the generalizability and clinical relevance of the results. Standardized laboratory conditions combined with reliable three-dimensional investigation approaches are necessary to obtain clinically informative findings.


Assuntos
Anti-Infecciosos , Camada de Esfregaço , Humanos , Quelantes/farmacologia , Anti-Infecciosos/farmacologia , Assistência Odontológica , Revisões Sistemáticas como Assunto
16.
ACS Appl Bio Mater ; 7(1): 246-255, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37967519

RESUMO

Antibacterial materials composed of biodegradable and biocompatible constituents that are produced via eco-friendly synthetic strategies will become an attractive alternative to antibiotics to combat antibiotic-resistant bacteria. In this study, we demonstrated the antibacterial properties of nanosheet-shaped crystalline assemblies of enzymatically synthesized aminated cellulose oligomers (namely, surface-aminated synthetic nanocelluloses) and their synergy with a metal-chelating antibacterial agent, ethylenediaminetetraacetic acid (EDTA). Growth curves and colony counting assays revealed that the surface-aminated cellulose assemblies had an antibacterial effect against Gram-negative Escherichia coli (E. coli). The cationic assemblies appeared to destabilize the cell wall of E. coli through electrostatic interactions with anionic lipopolysaccharide (LPS) molecules on the outer membrane. The antibacterial properties were significantly enhanced by the concurrent use of EDTA, which potentially removed metal ions from LPS molecules, resulting in synergistic bactericidal effects. No antibacterial activity of the surface-aminated cellulose assemblies was observed against Gram-positive Staphylococcus aureus even in the presence of EDTA, further supporting the contribution of electrostatic interactions between the cationic assemblies and anionic LPS to the activity against Gram-negative bacteria. Analysis using quartz crystal microbalance with dissipation monitoring revealed the attractive interaction of the surface-aminated cellulose assembly with LPS Ra monolayers artificially produced on the device substrate.


Assuntos
Escherichia coli , Lipopolissacarídeos , Ácido Edético/farmacologia , Lipopolissacarídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Quelantes/farmacologia , Metais , Cátions , Celulose/farmacologia
17.
Tree Physiol ; 44(1)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-37756614

RESUMO

Heavy metal pollution of soil, especially by lead (Pb) and cadmium (Cd), is a serious problem worldwide. The application of safe chelating agents, combined with the growing of tolerant trees, constitutes an approach for phytoremediation of heavy-metal-contaminated soil. This study aimed to determine whether the two safe chelators, tetrasodium glutamate diacetate (GLDA) and citric acid (CA), could improve the phytoremediation capacity of black locust (Robinia pseudoacacia L.) in a Pb-Cd-contaminated soil and to find the key factors affecting the biomass accumulation of stressed black locust. In Pb- and Cd-stressed black locust plants, medium- and high-concentration GLDA treatment inhibited the growth, chlorophyll synthesis and maximum photochemical efficiency (Fv/Fm), promoted the absorption of Pb and Cd ions and resulted in the shrinkage of chloroplasts and starch grains when compared with those in Pb- and Cd-stressed plants that were not treated with GLDA. The effects of CA on plant growth, ion absorption, chlorophyll content, chlorophyll fluorescence and organelle size were significantly weaker than those of GLDA. The effect of both agents on Cd absorption was greater than that on Pb absorption in all treatments. The levels of chlorophyll a and plant tissue Cd and rates of starch metabolism were identified as the key factors affecting plant biomass accumulation in GLDA and CA treatments. In the future, GLDA can be combined with functional bacteria and/or growth promoters to promote the growth of Pb- and Cd-stressed plants and to further improve the soil restoration efficiency following pollution by heavy metals. Application of CA combined with the growing of black locust plants has great potential for restoring the Cd-polluted soil. These findings also provide insights into the practical use of GLDA and CA in phytoremediation by R. pseudoacacia and the tolerant mechanisms of R. pseudoacacia to Pb-Cd-contaminated soil.


Assuntos
Metais Pesados , Robinia , Cádmio/metabolismo , Plântula , Quelantes/metabolismo , Quelantes/farmacologia , Clorofila A/metabolismo , Clorofila A/farmacologia , Chumbo/metabolismo , Metais Pesados/metabolismo , Clorofila/metabolismo , Solo/química , Amido/metabolismo , Biodegradação Ambiental
18.
Biochim Biophys Acta Mol Cell Res ; 1871(2): 119589, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37739271

RESUMO

Intracellular Ca2+ signals play a vital role in a broad range of cell biological and physiological processes in all eukaryotic cell types. Dysregulation of Ca2+ signaling has been implicated in numerous human diseases. Over the past four decades, the understanding of how cells use Ca2+ as a messenger has flourished, largely because of the development of reporters that enable visualization of Ca2+ signals in different cellular compartments, and tools that can modulate cellular Ca2+ signaling. One such tool that is frequently used is BAPTA; a fast, high-affinity Ca2+-chelating molecule. By making use of a cell-permeable acetoxymethyl ester (AM) variant, BAPTA can be readily loaded into the cytosol of cells (referred to as BAPTAi), where it is trapped and able to buffer changes in cytosolic Ca2+. Due to the ease of loading of the AM version of BAPTA, this reagent has been used in hundreds of studies to probe the role of Ca2+ signaling in specific processes. As such, for decades, researchers have almost universally attributed changes in biological processes caused by BAPTAi to the involvement of Ca2+ signaling. However, BAPTAi has often been used without any form of control, and in many cases has neither been shown to be retained in cells for the duration of experiments nor to buffer any Ca2+ signals. Moreover, increasing evidence points to off-target cellular effects of BAPTA that are clearly not related to Ca2+ chelation. Here, we briefly introduce Ca2+ signaling and the history of Ca2+ chelators and fluorescent Ca2+ indicators. We highlight Ca2+-independent effects of BAPTAi on a broad range of molecular targets and describe some of BAPTAi's impacts on cell functions that occur independently of its Ca2+-chelating properties. Finally, we propose strategies for determining whether Ca2+ chelation, the binding of other metal ions, or off-target interactions with cell components are responsible for BAPTAi's effect on a particular process and suggest some future research directions.


Assuntos
Quelantes , Humanos , Ácido Egtázico/farmacologia , Quelantes/farmacologia , Citosol
19.
Eur Endod J ; 9(1): 73-80, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38157281

RESUMO

OBJECTIVE: Irrigating solutions play an important role in the debridement and disinfection of the root canal space, and thus, it is crucial to comprehend their effects on the composition and surface structure of radicular dentine. This study evaluated and compared the effects of 17% ethylenediaminetetraacetic acid (EDTA), 9% 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) and 0.2% chitosan on the mineral content and erosion of radicular dentine when used as a final rinse. METHODS: Sixty extracted human mandibular premolar teeth were decoronated and instrumented to ProTaper size F2. After final instrumentation, the samples were randomly divided into 4 groups (n=15) according to the type of final irrigant used: Normal saline (control), 17% EDTA, 9% HEBP and 0.2% chitosan. Field emission scanning electron microscopy was used to assess the erosion of radicular dentine, and energy dispersive X- ray spectroscopy was used to quantify the radicular dentine mineral composition at the coronal, middle and apical levels of all the prepared samples after final irrigation. The one-way analysis of variance was used for intra-group and inter-group comparisons of means, the Kruskal Wallis test for intra-group and inter-group comparisons of medians and Tukey's post hoc test for pairwise comparisons. RESULTS: There was no significant difference in the levels of calcium (Ca), phosphorus (P) and Ca/P ratio after final rinse with 17% EDTA, 9% HEBP and 0.2% chitosan at all three root levels (p>0.05); except at the coronal level, where 0.2% chitosan caused significantly less alteration in Ca levels and Ca/P ratio than 17% EDTA and 9% HEBP respectively (p<0.05). 17% EDTA, 9% HEBP and 0.2% chitosan caused no erosion at the middle and apical levels. Meanwhile, 17% EDTA and 9% HEBP caused moderate erosion at the coronal level. CONCLUSION: Alternatives to 17% EDTA during final irrigation can be 9% HEBP and 0.2% chitosan. (EEJ-2023-06-078).


Assuntos
Quelantes , Quitosana , Humanos , Quelantes/análise , Quelantes/farmacologia , Quitosana/análise , Quitosana/farmacologia , Cavidade Pulpar , Dentina/química , Difosfonatos/análise , Difosfonatos/farmacologia , Ácido Edético/análise , Ácido Edético/farmacologia , Minerais/análise , Minerais/farmacologia
20.
Chemosphere ; 350: 141066, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159731

RESUMO

Radionuclide uranium is a great threat to human health, due to its high chemical toxicity and radioactivity. Finding suitable uranium decorporation to reduce damage caused by uranium internal contamination is an important aspect of nuclear emergency response. However, the poor selectivity and/or high toxicity of the only excretory promoter approved by Food and Drug Administration (FDA) is an obvious disadvantage. Herein, we choose an edible natural product, the traditional Chinese medicine called Perilla frutescens (PF), which has wide sources and can be used as an excellent and effective uranyl decorporation. In vivo uranium decorporation assays illustrate the removal efficiency of uranium in kidney were 68.87% and 43.26%, in femur were 56.66% and 54.53%, by the test of prophylactic and immediate administration, respectively. Cell level experiments confirmed that it had better biocompatibility than CaNa3-DTPA (CaNa3-diethylenetriamine pentaacetate, a commercial actinide excretion agent). In vitro static adsorption experiments exhibited that its excellent selectivity sorption for uranyl. All those results findings would provide new research insights about natural product for uranyl decorporation.


Assuntos
Produtos Biológicos , Perilla frutescens , Urânio , Humanos , Urânio/toxicidade , Quelantes/farmacologia , Rim , Produtos Biológicos/farmacologia
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