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1.
Bioorg Chem ; 125: 105844, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35594720

RESUMO

A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC50 > 100 µM; eqBChE IC50 = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.

2.
Anal Chem ; 94(19): 7029-7034, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35512314

RESUMO

The development of online surface-enhanced Raman spectroscopy (SERS) detection methods is crucial to achieving high-throughput efficiency. Herein, a non-noble-metal moving substrate that integrates the functions of enrichment and sensing is developed for the microfluidic online-high-throughput detection of pollutants. The lowest limit of detection of 1 × 10-12 M and a Raman enhancement factor of 6.3 × 108 are obtained on the nanospheres. In a single detection channel, the analysis of 20 samples is achieved within 5 min, and the relative standard deviation of the signals is less than 6.8%. Compared with static SERS detection of fixed substrates, this dynamic SERS detection method greatly reduces the contamination memory effect of the analyte residue, enabling it to perform the sequential quantitative detection of samples with large concentration differences. Moreover, the current online SERS platform realizes the rapid quantitative detection of multicomponent samples.

3.
ACS Nano ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023714

RESUMO

Looking for high-performance substrates is an important goal of current surface enhanced Raman scattering (SERS) research. Herein, ultrathin multilayer rhenium (Re) nanosheets as a rare-earth metal substrate are found to have extraordinary SERS performance. These Re nanosheets are prepared through a convenient low-temperature molten salt strategy, and their total thickness is ∼5 nm, including 3-4 layers of ultrathin nanosheets with a thickness of only ∼1 nm. The viscosity of molten salt plays a key role in the formation of these ultrathin layered nanosheets. These nanosheets exhibit a strong and well-defined localized surface plasmon resonance (SPR) effect in the visible light region. The plasmonic Re nanosheets show excellent SERS performance with high sensitivity, chemical stability, and signal repeatability. The lowest detection limit for toxic compounds is 10-12 mol, and the corresponding Raman enhancement factor is 9.1 × 108. A composite enhancement mechanism caused by localized-SPR and charge transport has played an important role in the rare-earth-SERS. High-throughput multiassay analysis is performed on the flexible membrane assembled from the Re nanosheets, which highlights that our system is capable of rapid separation and identification of the samples containing various analytes.

4.
Eur J Med Chem ; 228: 113960, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34774339

RESUMO

Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Quinazolinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Quinazolinas/síntese química , Quinazolinas/química , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade
5.
Eur J Med Chem ; 227: 113888, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34628244

RESUMO

Although gastric cancer has become a major public health problem, oral agents applied in clinics for gastric cancer therapy are scarce. Therefore, to explore new oral chemical entities with high efficiency and low toxicity, 41 o-aminobenzamide derivatives based on the scaffolds of MS-275 and SAHA were designed, synthesized, and evaluated for their anti-gastric cancer abilities in vitro and in vivo. Structure-activity relationships were discussed, leading to the identification of compounds F8 (IC50 = 0.28 µM against HGC-27 cell) and T9 (IC50 = 1.84 µM against HGC-27 cell) with improved cytotoxicity, anti-gastric cancer proliferation potency, induction of cell apoptosis and cell cycle arrest ability, inhibition of cell migration and invasion. What is worth mentioning is that compound F8 was more efficient and less toxic than the positive drug capecitabine in vivo on the HGC-27-xenograft model. Meanwhile, compound F8 exhibited suitable pharmacokinetic properties and less acute toxicity (LD50 > 1000 mg/kg). Besides, western blotting analysis, IHC analysis, differentially expressed proteins analysis and ABPP experiment indicated that compound F8 could modulate molecular pathways involved in apoptosis and cell cycle progression. Consequently, compound F8 is a strong candidate for the development of human gastric cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Desenho de Fármacos , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzamidas/síntese química , Benzamidas/química , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Células Tumorais Cultivadas
6.
Eur J Med Chem ; 227: 113908, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34656900

RESUMO

Highly efficacious and tolerable agents for the treatment of glioblastoma (GBM), the most common and aggressive primary brain tumor, are urgently needed. Herein, we reveal the design, synthesis and biological evaluation of several piperazine based benzamide derivatives, which are based on the non-classical isostere principle and combination principle for GBM therapy. After structure-activity relationship (SAR) study, compound L19 was demonstrated as the most promising compound with IC50 values of 0.15 µM, 0.29 µM, 1.25 µM against GBM C6, U87-MG, U251 cells, respectively. Moreover, compound L19 could inhibit the proliferation, migration and invasion, as well as induce apoptosis and cell cycle arrest of GBM cell lines in vitro. From mechanism perspective, compound L19 could regulate the cell cycle-related proteins and influence the p16INK4a-CDK4/6-pRb pathway by western blotting experiment. What is worth mentioning is that compound L19 could penetrate the blood-brain barrier (BBB) with an exceptional brain-to-plasma ratio of 1.07 in vivo. Besides, the superior anti-glioblastoma potency in vivo of compound L19 was identified on U87-MG-xenograft model without any apparent host toxicity. Overall, the potential of compound L19 warrants further pre-clinical investigation for GBM therapy.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Glioblastoma/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Piperazinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/metabolismo , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Piperazinas/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Células Tumorais Cultivadas
7.
Eur J Med Chem ; 229: 114044, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34923430

RESUMO

In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-α, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Aß1-42. Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.


Assuntos
Carbamatos/química , Desenho de Fármacos , Fármacos Neuroprotetores/síntese química , Triptaminas/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Sítios de Ligação , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Carbamatos/metabolismo , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Agregados Proteicos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
8.
ACS Omega ; 6(48): 32879-32887, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34901638

RESUMO

Poly(vinylpyrrolidone) (PVP) was used as both a modifier and reductant to in situ deposit silver nanoparticles (denoted Ag NPs) on the surface of silica nanospheres (nanosilica or nano-SiO2), affording Ag-decorated nanosilica (denoted SiO2@Ag). The as-obtained SiO2@Ag composite can form silver nanoparticle-decorated silica nanosphere arrays (denoted SiO2@Ag arrays) via evaporation-induced self-assembly. The as-prepared SiO2@Ag composite and SiO2@Ag array were used as the SERS substrates to measure the Raman signals of the dilute solutions of rhodamine 6G (denoted R6G), an organic dye that is a potential pollutant to the environment. The findings indicate that the as-prepared SiO2@Ag composite and SiO2@Ag array as potential SERS substrates simultaneously exhibit a high degree of metal coverage and small size of Ag NPs as well as good stability and abundant "hot spots", which contributes to their desired Raman enhancement capacities. For the detection of trace R6G, they provide a limit of detection of as low as 10-9-10-11 M as well as good reproducibility, showing promising potential for monitoring chemical and biological molecules.

9.
Nat Commun ; 12(1): 6283, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725330

RESUMO

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

10.
Eur J Med Chem ; 226: 113817, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34537445

RESUMO

Glioblastoma is one of the most lethal brain tumors. The crucial chemotherapy is mainly alkylating agents with modest clinical success. Given this desperate need and inspired by the encouraging results of a phase II trial via concomitant Topo I inhibitor plus COX-2 inhibitor, we designed a series of N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents based on structure modification on 1,5-naphthyridine derivatives (Topo I inhibitors). Notably, the target compounds I-1 (33.61 ± 1.15 µM) and I-8 (45.01 ± 2.37 µM) were confirmed to inhibit COX-2, while a previous reported compound (1,5-naphthyridine derivative) resulted nearly inactive towards COX-2 (IC50 > 150 µM). Besides, I-1 and I-8 exhibited higher anti-proliferation, anti-migration, anti-invasion effects than the parent compound 1,5-naphthyridine derivative, suggesting the success of modification based on the parent. Moreover, I-1 obviously repressed tumor growth in the C6 glioma orthotopic model (TGI = 66.7%) and U87MG xenograft model (TGI = 69.4%). Besides, I-1 downregulated PGE2, VEGF, MMP-9, and STAT3 activation, upregulated E-cadherin in the orthotopic model. More importantly, I-1 showed higher safety than temozolomide and different mechanism from temozolomide in the C6 glioma orthotopic model. All the evidence demonstrated that N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents could be promising for the glioma management.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Inibidores da Topoisomerase/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzamidas/síntese química , Benzamidas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/química , Células Tumorais Cultivadas
11.
Anal Chem ; 93(36): 12360-12366, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34472338

RESUMO

Facing the complex environment of on-site detection, the development of active substrates with wide-spectrum surface-enhanced Raman scattering (SERS) activity is essential. Herein, we report on the low temperature and reproducible synthesis of plasmonic δ-MoN yolk microspheres by in situ-nitriding amorphous MoO2 microspheres at 500 °C and 1 atm. The yolk-structured δ-MoN exhibits strong and wide-spectrum surface plasmon resonance and SERS effects and can perform highly selective detection for probes with different absorption wavelengths under excitation of 532, 633, and 785 nm lasers, with a limitation of 10-11 M and an enhanced factor of 3.6 × 107. Moreover, the plasmonic δ-MoN yolk microspheres have high environmental durability, which can maintain high sensitivity in strong acid and alkaline solutions.


Assuntos
Análise Espectral Raman , Ressonância de Plasmônio de Superfície , Microesferas
12.
Bioorg Chem ; 114: 105154, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34378540

RESUMO

Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-ß/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Desenho de Fármacos , Neoplasias Hepáticas/tratamento farmacológico , Quinazolinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Nus , Estrutura Molecular , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
Eur J Med Chem ; 222: 113564, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34091208

RESUMO

COX-2 and STAT3 are two key culprits in the glioma microenvironment. Herein, to inhibit COX-2 and block STAT3 signaling, we disclosed 27 N-anthraniloyl tryptamine compounds based on the combination of melatonin derivatives and N-substituted anthranilic acid derivatives. Among them, NP16 showed the best antiproliferative activity and moderate COX-2 inhibition. Of note, NP16 decreased the level of p-JAK2 and p-STAT3, and blocked the nuclear translocation of STAT3 in GBM cell lines. Moreover, NP16 downregulated the MMP-9 expression of BV2 cells in a co-culture system of BV2 and C6 glioma cells, abrogated the proliferative/invasive/migratory abilities of GBM cells, induced apoptosis by ROS and the Bcl-2-regulated apoptotic pathway, and induced obvious G2/M arrest in glioma cells in vitro. Furthermore, NP16 displayed favorable pharmacokinetic profiles covering long half-life (11.43 ± 0.43 h) and high blood-brain barrier permeability. Finally, NP16 effectively inhibited tumor growth, promoted the survival rate, increased the expression of E-cadherin and reduced overproduction of PGE2, MMP-9, VEGF-A and the level of p-STAT3 in tumor tissue, and improved the anxiety-like behavior in C6 glioma model. All these evidences demonstrated N-anthraniloyl tryptamine derivatives as multifunctional anti-glioma agents with high potency could drain the swamp to beat glioma.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Glioma/tratamento farmacológico , Triptaminas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/metabolismo , Glioma/patologia , Humanos , Estrutura Molecular , Ratos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Triptaminas/síntese química , Triptaminas/química , Células Tumorais Cultivadas
14.
Soft Matter ; 17(25): 6081-6087, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34109344

RESUMO

Chain entanglement behaviors were studied by 1H Hahn echo nuclear magnetic resonance (NMR) and 1H double-quantum (DQ) NMR experiments. Poly(ethylene oxide) (PEO) was chosen to investigate the chain entanglement behaviors. The 1H Hahn echo NMR results demonstrate that the critical molecular weight of PEO is approximately 6 kg mol-1. Above this critical molecular weight, chain entanglements start to occur in the melts resulting in anisotropic motions of polymer chain. The 1H DQ NMR observations establish that PEO melts with molecular weights above the critical value exhibit dynamical entanglements. The entangled networks, formed by PEO with a molecular weight of 480 kg mol-1 (PEO480), present slow mobility and rather homogeneously distributed chain entanglements, while the entangled networks, formed by PEO with a molecular weight of 255 kg mol-1 (PEO255), present fast mobility and obvious dynamic heterogeneity in the distribution of chain entanglement. Short chain PEOs like that with a molecular weight of 2 kg mol-1 are demonstrated to function like solvents when being added in an appropriate concentration to PEO480, and the dilution effect increases the chain mobility of PEO480. Moreover, properly diluted PEO480 networks exhibit dynamic heterogeneity similar to that observed in PEO255.

15.
Nano Lett ; 21(10): 4410-4414, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33970632

RESUMO

γ-Mo2N and δ-MoN are the two most important molybdenum nitrides, but controllable preparation of them with high surface area has not been achieved. Herein, we achieved selective preparation of γ-Mo2N and δ-MoN. The key factor for the selective preparation of γ-Mo2N and δ-MoN is to control the crystal phase of the precursor MoO3. In H2O and NH3 mixed gas, the α-MoO3 nanoribbons are nitridated to obtain γ-Mo2N single-crystal porous nanobelts, while the h-MoO3 prisms are nitrided to obtain δ-MoN hierarchical porous columns. The corrosion effect of H2O plays a key role in the formation of single-crystal porous structure. The γ-Mo2N flexible membrane composed of the single-crystal porous nanobelts exhibits strong localized surface plasmon resonance and surface enhanced Raman scattering effect, which show highly sensitive response to polychlorinated phenol.

16.
Bioorg Med Chem Lett ; 44: 128106, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991630

RESUMO

Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure-activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC50 = 0.010 µM) and the activity of iNOS (IC50 = 0.082 µM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future.


Assuntos
Amidas/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Descoberta de Drogas , Inflamação/tratamento farmacológico , Óxido Nítrico/antagonistas & inibidores , Doença Aguda , Amidas/síntese química , Amidas/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Carragenina , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Relação Estrutura-Atividade
17.
Bioorg Chem ; 111: 104828, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33895605

RESUMO

Marine natural products derived from special or extreme environment provide an important source for the development of anti-tumor drugs due to their special skeletons and functional groups. In this study, based on our previous work on the total synthesis and structure revision of the novel marine natural product Chrysamide B, a group of its derivatives were designed, synthesized, and subsequently of which the anti-cancer activity, structure-activity relationships and cellular mechanism were explored for the first time. Compared with Chrysamide B, better anti-cancer performance of some derivatives against five human cancer cell lines (SGC-7901, MGC-803, HepG2, HCT-116, MCF-7) was observed, especially for compound b-9 on MGC-803 and SGC-7901 cells with the IC 50 values of 7.88 ± 0.81 and 10.08 ± 1.08 µM, respectively. Subsequently, cellular mechanism study suggested that compound b-9 treatment could inhibit the cellular proliferation, reduce the migration and invasion ability of cells, and induce mitochondrial-dependent apoptosis in gastric cancer MGC-803 and SGC-7901 cells. Furthermore, the mitochondrial-dependent apoptosis induced by compound b-9 is related with the JAK2/STAT3/Bcl-2 signaling pathway. To conclude, our results offer a new structure for the discovery of anti-tumor lead compounds from marine natural products.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Desenho de Fármacos , Amidas/síntese química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Compostos Bicíclicos com Pontes/síntese química , Compostos Bicíclicos com Pontes/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
18.
J Pharm Biomed Anal ; 195: 113820, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33303266

RESUMO

The current study presents a comprehensive analysis to explore the compositions of both the supernatant and naturally-occurring precipitate of Huanglian Jiedu decoction employing ultra-high-performance liquid chromatography hyphenated with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Totally 109 constituents (32 alkaloids, 39 flavonoids, 12 iridoids, 9 phenolic acids, and 17 other compounds) were identified from accurate-mass measurements in full-scan MS/data-dependent MS/MS mode of acquisition. Furthermore, a quantitative method was developed for determination of 14 marker compounds in Huanglian Jiedu decoction. Experimental results revealed that all of these marker compounds were present in both the supernatant and naturally-occurring precipitate. Most notably, the contents of baicalin and berberine were significantly higher in the naturally-occurring precipitate than supernatant, presumably due to self-assembly complexation. The formation of the baicalin/berberine complex was comprehensively investigated by electrospray ionization (ESI)-MS, nuclear magnetic resonance (NMR), ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), and fluorescence spectroscopy, etc. The morphology and size distribution of the baicalin/berberine self-assembled nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). This study provides fundamental scientific evidence of the presence of a self-assembled phytochemical complex in the naturally-occurring precipitate, enabling better understanding of Huanglian Jiedu decoction.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos
19.
Front Pharmacol ; 12: 754366, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35185534

RESUMO

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

20.
ACS Nano ; 14(10): 13718-13726, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-32931250

RESUMO

MoN and Mo2C are important functional materials; however, due to the high activation energy barrier in their nucleation, their synthesis generally requires harsh conditions such as high temperature (>1000 °C) and high pressure (several GPa). The extreme conditions also hinder the acquisition of their ultrafine nanostructures. Herein, we report that MoN and Mo2C hollow spheres with large surface area (108.7-125.6 m2 g-1) and ultrafine nanoparticles (2-5 nm) are prepared by a quasi-metal-based microwave route under mild conditions. MoO2 hollow spheres are used as a quasi-metallic microwave absorbing medium as well as a molybdenum source and template simultaneously. The MoN and Mo2C ultrafine nanocrystalline hollow spheres exhibit strong localized surface plasmon resonance, high photothermal conversion efficiency, and strong surface-enhanced Raman scattering effects. Highly crystalline MoS2 nanosheet hollow spheres can also be obtained by this method, indicating its universality. The present work provides an effective strategy for the rapid and mild preparation of ultrafine nanocrystalline transition metal nitrides and carbides with ultrahigh activation energy.

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