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1.
Biopolymers ; 115(3): e23574, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38469937

RESUMO

Nucleophilic moieties in polysaccharides (PS) with distinct higher reactivity compared with the hydroxy group are interesting for sustainable applications in chemistry, medicine, and pharmacy. An efficient heterogeneous method for the formation of such nucleophilic PS is described. Employing alcohols as slurry medium, protonated carboxymethyl (CM) PS and hydrazine hydrate are allowed to react at elevated temperatures. The CM derivatives of starch and pullulan can be transformed almost quantitatively to the corresponding hydrazides. The reaction is less efficient for CM dextrans and CM xylans. As slurry media, 2-propanol and ethanol were probed, and the results are compared with a homogeneous procedure performed in water. Overall, the heterogeneous procedure is superior compared with the homogeneous route. 2-Propanol is the best slurry medium investigated yielding PS hydrazides with the highest nitrogen content.


Assuntos
Hidrazinas , Polissacarídeos , Hidrazinas/química , Polissacarídeos/química , Polissacarídeos/síntese química , Glucanos/química , Glucanos/síntese química , Amido/química , Amido/análogos & derivados , Amido/síntese química , 2-Propanol/química , Dextranos/química , Dextranos/síntese química , Etanol/química , Xilanos/química
2.
BMC Cardiovasc Disord ; 24(1): 169, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509468

RESUMO

Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and - 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.


Assuntos
Aneurisma , Inflamação , Animais , Coelhos , Inflamação/patologia , Imageamento por Ressonância Magnética , Peroxidase , Artérias
3.
Mol Divers ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926303

RESUMO

Succinate dehydrogenase inhibitors (SDHIs) as one of the fastest-growing fungicide categories for plant protection. In this study, a series of N'-phenyl pyridylcarbohydrazides as analogues of commercial SDHIs were designed and evaluated for inhibition activity on phytopathogenic fungi to search for potential novel SDHIs. The determination of antifungal activity in vitro and in vivo led to the discovery of a series of compounds with high activity and broad-spectrum property. Especially, N'-(4-fluorophenyl)picolinohydrazide (1c) and N'-(3,4-fluorophenyl)picolinohydrazide (1ae) showed 0.041-1.851 µg/mL of EC50 values on twelve fungi, superior to positive controls carbendazim and boscalid. In vivo activity, 1c at 50 µg/mL showed 61% of control efficacy at the post-treatment 9th day for the infection of P. piricola on apples, slightly smaller than 70% of carbendazim. In terms of action mechanism, 1c showed strong inhibition activity with IC50 of 0.107 µg/mL on SDH in Alternaria brassicae, superior to positive SDHI boscalid (IC50 0.182 µg/mL). Molecular docking indicated that 1c can well bind with the ubiquinone-binding region of SDH mainly by hydrogen bond, carbon hydrogen bond, π-alkyl, amide-π stacking, F-N and F-H interactions. Furthermore, scanning and transmission electron micrographs showed that 1c was able to obviously change the structure of mycelia and cell membrane. Fluorescence staining analysis showed that 1c could increase both the intracellular reactive oxygen species level and mitochondrial membrane potential. Finally, seed germination test, seedling growth test and cytotoxicity assay showed that 1c had very low toxicity to plant growth and mammalian cells. Thus, N'-phenyl pyridylcarbohydrazides especially 1c and 1ae can be considered promising fungicide alternatives for plant protection.

4.
Mol Divers ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141208

RESUMO

A series of novel sulfonyl hydrazide based ß-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC50 values being 2.12 ± 0.33-19.37 ± 1.49 µM. Compound SX29 with a para-phenyl (IC50: 2.12 ± 0.33 µM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 µM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based ß-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.

5.
Arch Pharm (Weinheim) ; : e2400562, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344558

RESUMO

This study describes the synthesis and characterization of a series of novel hydrazide-hydrazone derivatives containing a 1,2,4-triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT-116, HepG-2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl-xL inhibitory concentration (IC50) values. These compounds further demonstrated selective cytotoxicity against the Bcl-xL-dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl-xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl-xL. Overall, these results demonstrate the potential of these novel hydrazide-hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5-fluorouracil.

6.
Molecules ; 29(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38893377

RESUMO

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 µg/mL against G. zeae, EC50 = 1.01 µg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 µg/mL against A. alternata, EC50 = 0.20 µg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.


Assuntos
Antifúngicos , Testes de Sensibilidade Microbiana , Relação Quantitativa Estrutura-Atividade , Quinoxalinas , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Quinoxalinas/farmacologia , Quinoxalinas/química , Quinoxalinas/síntese química , Desenho de Fármacos , Alternaria/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Estrutura Molecular , Colletotrichum/efeitos dos fármacos , Gibberella/efeitos dos fármacos
7.
Molecules ; 29(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998972

RESUMO

Heterocyclic compounds, particularly those containing azole rings, have shown extensive biological activity, including anticancer, antibacterial, and antifungal properties. Among these, the imidazole ring stands out due to its diverse therapeutic potential. In the presented study, we designed and synthesized a series of imidazole derivatives to identify compounds with high biological potential. We focused on two groups: thiosemicarbazide derivatives and hydrazone derivatives. We synthesized these compounds using conventional methods and confirmed their structures via nuclear magnetic resonance spectroscopy (NMR), MS, and elemental analysis, and then assessed their antibacterial and antifungal activities in vitro using the broth microdilution method against Gram-positive and Gram-negative bacteria, as well as Candida spp. strains. Our results showed that thiosemicarbazide derivatives exhibited varied activity against Gram-positive bacteria, with MIC values ranging from 31.25 to 1000 µg/mL. The hydrazone derivatives, however, did not display significant antibacterial activity. These findings suggest that structural modifications can significantly influence the antimicrobial efficacy of imidazole derivatives, highlighting the potential of thiosemicarbazide derivatives as promising candidates for further development in antibacterial therapies. Additionally, the cytotoxic activity against four cancer cell lines was evaluated. Two derivatives of hydrazide-hydrazone showed moderate anticancer activity.


Assuntos
Antibacterianos , Antifúngicos , Antineoplásicos , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Humanos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Nitroimidazóis/farmacologia , Nitroimidazóis/química , Nitroimidazóis/síntese química , Linhagem Celular Tumoral , Bactérias Gram-Negativas/efeitos dos fármacos , Relação Estrutura-Atividade , Semicarbazidas/química , Semicarbazidas/farmacologia , Semicarbazidas/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Candida/efeitos dos fármacos , Estrutura Molecular
8.
Molecules ; 29(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38792153

RESUMO

Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.


Assuntos
Apoptose , Aziridinas , Neoplasias da Mama , Proliferação de Células , Tamoxifeno , Humanos , Tamoxifeno/farmacologia , Tamoxifeno/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Células MCF-7 , Feminino , Aziridinas/farmacologia , Aziridinas/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hidrazonas/farmacologia , Hidrazonas/química , Probióticos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos
9.
Molecules ; 29(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38398645

RESUMO

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

10.
Angew Chem Int Ed Engl ; : e202415510, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39158108

RESUMO

Nature has ingeniously developed specialized water transporters that effectively reject ions, including protons, while transporting water across membranes. These natural water channels, known as aquaporins (AQPs), have inspired the creation of Artificial Water Channels (AWCs). However, replicating superfast water transport with synthetic molecular structures that exclude salts and protons is a challenging task. This endeavor demands the coexistence of a suitable water-binding site and a selective filter for precise water transportation. Here, we present small-molecule hydrazides 1b-1d that self-assemble into a rosette-type nanochannel assembly through intermolecular hydrogen bonding and π-π stacking interactions, and selectively transport water molecules across lipid bilayer membranes. The experimental analysis demonstrates notable permeability rates for the 1c derivative, enabling approximately 3.18 × 108 water molecules to traverse the channel per second. This permeability rate is about one order of magnitude lower than that of AQPs. Of particular significance, the 1c ensures exclusive passage of water molecules while effectively blocking salts and protons. MD simulation studies confirmed the stability and water transport properties of the water channel assembly inside the bilayer membranes at ambient conditions.

11.
Angew Chem Int Ed Engl ; 63(14): e202317570, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38366960

RESUMO

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (SN2) at saturated carbon centers, analogous SN2 reaction at the amide nitrogen atom remains extremely limited. Here we report an SN2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis.

12.
Proteomics ; 23(3-4): e2100378, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35532377

RESUMO

Protein lysine monomethylation is an important post-translational modification participated in regulating many biological processes. There is growing interest in identifying these methylation events. However, the introduction of one methyl group on lysine residues has negligible effect on changing the physical and chemical properties of proteins or peptides, making enriching and identifying monomethylated lysine (Kme1) proteins or peptides extraordinarily challenging. In this study, we proposed an antibody-free chemical proteomics approach to capture Kme1 peptides from complex protein digest. By exploiting reductive glutaraldehydation, 5-aldehyde-pentanyl modified Kme1 residues and piperidine modified primary amines were generated at the same time. The peptides with aldehyde modified Kme1 residues were then enriched by solid-phase hydrazide chemistry. This chemical proteomics approach was validated by using several synthetic peptides. It was demonstrated that it can enrich and detect Kme1 peptide from peptide mixture containing 5000-fold more bovine serum albumin tryptic digest. Besides, we extended our approach to profile Kme1 using heavy methyl stable isotope labeling by amino acids in cell culture (hmSILAC) labeled Jurkat T cells and Hela cells. Totally, 29 Kme1 sites on 25 proteins were identified with high confidence and 11 Kme1 sites were identified in both two types cells. This is the first antibody-free chemical proteomics approach to enrich Kme1 peptides from complex protein digest, and it provides a potential avenue for the analysis of methylome.


Assuntos
Lisina , Proteoma , Humanos , Proteoma/metabolismo , Lisina/metabolismo , Células HeLa , Peptídeos/análise , Anticorpos , Aldeídos
13.
Biol Reprod ; 108(2): 204-217, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36308434

RESUMO

Uterine fluid plays important roles in supporting early pregnancy events and its timely absorption is critical for embryo implantation. In mice, its volume is maximum on day 0.5 post-coitum (D0.5) and approaches minimum upon embryo attachment ~D4.0. Its secretion and absorption in ovariectomized rodents were shown to be promoted by estrogen and progesterone (P4), respectively. The temporal mechanisms in preimplantation uterine fluid absorption remain to be elucidated. We have established an approach using intraluminally injected Alexa Fluor™ 488 Hydrazide (AH) in preimplantation control (RhoAf/f) and P4-deficient RhoAf/fPgrCre/+ mice. In control mice, bulk entry (seen as smeared cellular staining) via uterine luminal epithelium (LE) decreases from D0.5 to D3.5. In P4-deficient RhoAf/fPgrCre/+ mice, bulk entry on D0.5 and D3.5 is impaired. Exogenous P4 treatment on D1.5 and D2.5 increases bulk entry in D3.5 P4-deficient RhoAf/fPgrCre/+ LE, while progesterone receptor (PR) antagonist RU486 treatment on D1.5 and D2.5 diminishes bulk entry in D3.5 control LE. The abundance of autofluorescent apical fine dots, presumptively endocytic vesicles to reflect endocytosis, in the LE cells is generally increased from D0.5 to D3.5 but its regulation by exogenous P4 or RU486 is not obvious under our experimental setting. In the glandular epithelium (GE), bulk entry is rarely observed and green cellular dots do not show any consistent differences among all the investigated conditions. This study demonstrates the dominant role of LE but not GE, the temporal mechanisms of bulk entry and endocytosis in the LE, and the inhibitory effects of P4-deficiency and RU486 on bulk entry in the LE in preimplantation uterine fluid absorption.


Assuntos
Implantação do Embrião , Mifepristona , Gravidez , Feminino , Animais , Camundongos , Mifepristona/farmacologia , Implantação do Embrião/fisiologia , Progesterona/farmacologia , Estrogênios/farmacologia , Útero/fisiologia , Roedores
14.
Planta ; 257(3): 62, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36808312

RESUMO

MAIN CONCLUSION: Ammonium sulfate is well known to salt out proteins at high concentrations. The study revealed that it can serve to increase by 60% the total number of identified carbonylated proteins by LC-MS/MS. Protein carbonylation is a significant post-translational modification associated with reactive oxygen species signaling in animal and plant cells. However, the detection of carbonylated proteins involved in signaling is still challenging, as they only represent a small subset of the proteome in the absence of stress. In this study, we investigated the hypothesis that a prefractionation step with ammonium sulphate will improve the detection of the carbonylated proteins in a plant extract. For this, we extracted total protein from the Arabidopsis thaliana leaves and subjected the extract to stepwise precipitation with ammonium sulfate to 40%, 60%, and 80% saturation. The protein fractions were then analyzed by liquid chromatography-tandem mass spectrometry for protein identification. We found that all the proteins identified in the non-fractionated samples were also found in the prefractionated samples, indicating no loss was incurred during the prefractionation. About 45% more proteins were identified in the fractionated samples compared to the non-fractionated total crude extract. When the prefractionation steps were combined with the enrichment of carbonylated proteins labeled with a fluorescent hydrazide probe, several carbonylated proteins, which were unseen in the non-fractionated samples, became visible in the prefractionated samples. Consistently, the prefractionation method allowed to identify 63% more carbonylated proteins by mass spectrometry compared to the number of carbonylated proteins identified from the total crude extract without prefractionation. These results indicated that the ammonium sulfate-based proteome prefractionation can be used to improve proteome coverage and identification of carbonylated proteins from a complex proteome sample.


Assuntos
Arabidopsis , Proteoma , Animais , Sulfato de Amônio , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos
15.
Chemistry ; 29(38): e202300969, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37098764

RESUMO

Energy dissipation based on dynamic fracture of metal ligands is an effective way to toughen hydrogels for specific applications in biomedical and engineering fields. Exploration of new kinds of metal-ligand coordinates with robust bonding strength is crucial for the facile synthesis of tough gels. Here a hydrogel toughening strategy based on the formation of robust coordination complexes between the hydrazide ligands and zinc ions is reported. The resultant hydrogels exhibit high strength and toughness at room temperature. Their mechanical properties show temperature dependence due to the dynamic nature of coordination bonds. In addition, the amine group of hydrazides in the gel matrix provides a reactive site for Schiff's base reaction, enabling surface modification without influence on overall mechanical performances of the gel. The hydrazide ligands are easy to synthesize and can coordinate very well with several transition metals. Such a metal-ligand coordination should be suitable to develop tough soft materials with versatile applications.


Assuntos
Complexos de Coordenação , Hidrogéis , Hidrogéis/química , Ligantes , Hidrazinas , Metais , Zinco
16.
J Magn Reson Imaging ; 58(6): 1714-1722, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37078554

RESUMO

BACKGROUND: A novel myeloperoxidase-activatable manganese-based (MPO-Mn) MRI probe may enable the activation state of inflammatory foci to be detected and monitored noninvasively. PURPOSE: To evaluate the inflammatory response in a mouse model of acute gout using MPO as an imaging biomarker and a potential therapeutic target. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 40 male Swiss mice with monosodium urate crystals induced acute gout. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging with 2D fast spoiled gradient recalled echo and T2-weighted imaging with fast recovery fast spin-echo sequences. ASSESSMENT: The difference in contrast-to-noise ratio between left hind limb (lesion) and right hind limb (internal reference) (ΔCNR), and normalized signal-to-noise ratio (nSNR) on the right hind limb were calculated and compared. The expression level and activity of myeloperoxidase (MPO) were analyzed using western blotting and spectrophotometric quantitation activity assay. MPO-positive cell infiltration and lesion volume were evaluated using immunofluorescence staining and T2-weighted images, respectively. STATISTICAL TESTS: Student's t test. A P-value less than 0.05 was considered to be statistically significant. RESULTS: MPO-Mn resulted in a significantly higher ΔCNR than Gd-DTPA (22.54 ± 1.86 vs. 13.90 ± 2.22) but lower nSNR on the reference right hind limb (1.08 ± 0.07 vs. 1.21 ± 0.08). Compared to the nontreatment group, MPO-inhibition resulted in a significantly reduced contrast enhancement at the lesion (17.81 ± 1.58 vs. 22.96 ± 3.12), which was consistent with a remission of the inflammatory response, as evidenced by a substantial reduction of lesion volume (0.55 ± 0.16 mm3 /g vs. 1.14 ± 0.15 mm3 /g), myeloperoxidase expression level (0.98 ± 0.09 vs. 1.48 ± 0.19) and activity (0.75 ± 0.12 vs. 1.12 ± 0.07), and inflammatory cell recruitment. DATA CONCLUSION: MPO-Mn MRI has potential to evaluate the activation state of inflammatory foci in the experimental model of acute gout. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 1.


Assuntos
Meios de Contraste , Gota , Masculino , Animais , Camundongos , Peroxidase/metabolismo , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Gota/diagnóstico por imagem
17.
Photochem Photobiol Sci ; 22(8): 1933-1943, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37083995

RESUMO

A highly selective turn-on sensor for paramagnetic Fe3+ ions based on (E)-N'-((2-aminophenyl)(phenyl)methylene)thiophene-2-carbohydrazide is successfully synthesized. The sensor BPTH is significantly selective and sensitive towards Fe3+ ions over other interfering metal ions especially Cu2+ and Co2+ ions with a lowest limit of recognition 1.48 × 10-7 M. The turn-on sensing mechanism involves enhanced charge transfer. Fe3+ ion forms strong binding with the ligand with a Ka value about 8.23 × 104 M-1 and a 1:1 stoichiometric ratio is confirmed by Job's plot experiment. With Fe3+ ion, the yellow ligand BPTH change to a green fluorescent and reversible with 1 equivalent of EDTA. Practical application of sensor is demonstrated in real sample analysis.

18.
J Fluoresc ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37924382

RESUMO

Al3+ excess in the body can cause many diseases. The development of chemosensors for the detection of Al3+ is therefore highly desirable. A hydrazide Schiff base compound containing triphenylphosphonium units (ER) was prepared and used as fluorescence turn-on sensor for the sensing of Al3+. Detection of Al3+ among various metals has been achieved successfully through the formation of Al3+-ligand coordination complexes. To detect Al3+, the "turn on" property of the fluorogenic chemosensor was investigated. Fluorescence sensing studies were carried out in CH3OH-Water (v/v, 9/1, pH 7.0) at λem = 528 nm. The LOD for sensing of Al3+ was found to be 0.129 µM. Using Job's graph, the stoichiometric ratio of ER- Al3+ was determined to be 1:1. The binding constant was determined to be 1.7 × 107 M-1 between Al3 + and the chemosensor ER. Finally, the determination of Al3+ in real herbal teas was carried out by using the sensing function of the chemosensor ER.

19.
Macromol Rapid Commun ; 44(15): e2300133, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37227035

RESUMO

The development of catalyst-free ester-based covalent adaptable networks (CANs) provides a new approach to achieve milder reaction conditions to reprocess thermoset resins. Despite recent advances, however, accelerating network rearrangements requires the introduction of hydroxyl groups into the network. In this study, disulfide bonds are introduced into the CANs to add new kinetically facile pathways to accelerate network rearrangement. Kinetic experiments using small molecule models of the CANs show that the presence of the disulfide bonds can accelerate transesterification. These insights are applied to synthesize new kinds of poly(ß-hydrazide disulfide esters) (PSHEs) using thioctic acyl hydrazine (TAH) as a precursor for ring-opening polymerization with the hydroxyl-free multifunctional acrylates. The PSHE CANs have lower relaxation times (505-652 s) than the polymer containing only ß-hydrazide esters (2903 s). The ring-opening polymerization of TAH improves the crosslinking density, heating resistance deformation temperature, and UV shielding performance of the PSHEs. Thus, this work provides a practical strategy to reduce the reprocessing temperatures of CANs.


Assuntos
Dissulfetos , Ésteres , Ésteres/química , Dissulfetos/química , Acrilatos , Hidrazinas
20.
Bioorg Chem ; 140: 106786, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37586131

RESUMO

Recent studies show that some metal ions, injure microbial cells in various ways due to membrane breakdown, protein malfunction, and oxidative stress. Metal complexes are suited for creating novel antibacterial medications due to their distinct mechanisms of action and the variety of three-dimensional geometries they can acquire. In this Perspective, the present study focused on new antibacterial strategies based on metal oleoyl amide complexes. Thus, oleoyl amides ligand (fatty hydroxamic acid and fatty hydrazide hydrate) with the transition metal ions named Ag (I), Co (II), Cu (II), Ni (II) and Sn (II) complexes were successfully synthesized in this study. The metals- oleoyl amide were characterized using elemental analysis, and fourier transforms infrared (FTIR) spectroscopy. The antibacterial effect of metals- oleoyl amide complexes was investigated for Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) by analysing minimum inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and scanning electron microscopy (SEM). The results showed that metal-oleoyl amide complexes have high antibacterial activity at low concentrations. This study inferred that metal oleoyl amide complexes could be utilised as a promising therapeutic antibacterial agent.


Assuntos
Complexos de Coordenação , Elementos de Transição , Complexos de Coordenação/farmacologia , Antibacterianos/farmacologia , Elementos de Transição/farmacologia , Metais , Testes de Sensibilidade Microbiana , Íons , Ligantes
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