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1.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
2.
Chem Asian J ; 14(23): 4160-4163, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31657112

RESUMO

Multifunctional nanoparticles were simply synthesized by mixing a TICT+AIE featured molecule (TPAPP-CHO) with PBS solution. The fluorescent (FL) dots entered the cells via energy-related endocytosis and were located in lysosome emitting green FL. This indicated that the nanoparticles were dissociated in the lysosome. Moreover, the synthesized nanoparticles (NPs) demonstrate potent cytotoxicity against human U87 glioblastoma cells by inducing cell apoptosis via triggering intracellular ROS overproduction.


Assuntos
Compostos de Anilina/toxicidade , Apoptose/efeitos dos fármacos , Benzaldeídos/toxicidade , Corantes Fluorescentes/química , Pontos Quânticos/toxicidade , Tiadiazóis/toxicidade , Compostos de Anilina/química , Compostos de Anilina/uso terapêutico , Benzaldeídos/química , Benzaldeídos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Tiadiazóis/química , Tiadiazóis/uso terapêutico
3.
J Agric Food Chem ; 67(45): 12357-12365, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31596575

RESUMO

A series of isothiazole, 1,2,3-thiadiazole, and thiazole-based cinnamamide morpholine derivatives were rationally designed, synthesized, characterized, and evaluated for their fungicidal activities. Bioassay indicated that a combination of 3,4-dichloroisothiazole active substructures with cinnamamide morpholine lead to significant improvement of in vivo antifungal activities of the target compounds; among them, compound 5a exhibited good fungicidal activity against Pseudoperonspera cubensis in vivo with an inhibition rate of 100% at 100 µg/mL. A field experiment indicated that the difference of efficacy between 5a (75.9%) and dimethomorph (77.1%) at 37.5 g ai/667 m2 was not significant; and 5a also exhibited good activity against Botrytis cinerea by triggering accumulation of PAL and NPR1 defense-related gene expression and the defense associated enzyme phenylalanine ammonia-lyase (PAL) expression on cucumber, rather than direct inhibition. These findings strongly supported that 3,4-dichloroisothiazole containing cinnamamide morpholine 5a not only showed good fungicidal activity against P. cubensis but also exhibited plant innate immunity stimulation activity as a promising fungicide candidate with both fungicidal activity and systemic acquired resistance.


Assuntos
Cinamatos/química , Fungicidas Industriais/síntese química , Tiadiazóis/química , Tiazóis/química , Botrytis/efeitos dos fármacos , Botrytis/crescimento & desenvolvimento , Cinamatos/farmacologia , Cucumis sativus/efeitos dos fármacos , Cucumis sativus/genética , Cucumis sativus/metabolismo , Cucumis sativus/microbiologia , Descoberta de Drogas , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Estrutura Molecular , Doenças das Plantas/microbiologia , Relação Estrutura-Atividade , Tiadiazóis/farmacologia
4.
J Agric Food Chem ; 67(42): 11577-11583, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31557026

RESUMO

Nanotechnology has provided a novel approach for the preparation of a safe and highly effective pesticide formulation. Thiazole-Zn, a widely used bactericide, was successfully prepared at nanoscale by an innovative approach of final synthesis process control. Its plausible formation mechanism based on restricted particle aggregation in a nanoreactor was elucidated. Then in order to assess the application performance of thiazole-Zn nanoparticle, the nanoformulation (NPF) was conveniently formulated. Interestingly, the physicochemical properties of NPF showed better than that of the commercial pesticide formulation (CPF) in dispersibility, wettability, spreadability, and stability. At the same time, the in vitro bioassay showed that the minimum inhibitory concentrations (MICs) of NPF against Xanthomonas oryzae pv Oryzae (XOO), Xanthomonas oryzae pv Oryzicola (XOC), Erwinia carotovora subsp. Carotovora (Jones) Holland (ECC), and Erwinia chrysanthemi pv Zeae (ECZ) were 46.88, 93.75, 93.75, and 375.00 mg/L, respectively, whereas those of CPF were 93.75, 375.00, 375.00, and 875.00 mg/L, respectively. Therefore, NPF exhibited stronger antibacterial activity against the above-mentioned pathogens. Moreover, NPF was more effective to bacterial blight of rice than CPF in field trial. As a conclusion, nanotechnology for pesticides by synthesis process control will have a potential in improving the utilization efficiency and relieving the corresponding environmental pollution.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Nanopartículas/química , Nanotecnologia/métodos , Tiadiazóis/química , Tiadiazóis/farmacologia , Erwinia/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Xanthomonas/efeitos dos fármacos
5.
Adv Mater ; 31(44): e1904447, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31523869

RESUMO

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal-to-background ratio (SBR) is highly desirable for the study and theranostics of vascular-related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long-wavelength absorption and aggregation-induced near-infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two-photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR-II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR-II excitation. This study highlights the importance of developing NIR-II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neoplasias/diagnóstico por imagem , Pirróis/química , Pontos Quânticos/química , Tiadiazóis/química , Animais , Encéfalo/irrigação sanguínea , Sobrevivência Celular , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Neoplasias/irrigação sanguínea , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição Tecidual
6.
Environ Sci Pollut Res Int ; 26(29): 30333-30347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31435910

RESUMO

An in vitro study was conducted to evaluate the effects of thidiazuron (TDZ) growth regulator and magnesium oxide (MgO) nanoparticles on radish (Raphanus sativus L.) under lead (Pb) stress. Effects of TDZ and MgO on seed germination, growth, biomass, total phenolics and flavonoids, antioxidant potential, and Pb phytoaccumulation in different plant parts were assessed. Nanoparticles of MgO were synthesized with leaf extract of Sageretia thea (Osbeck) plant. Thidiazuron and MgO nanoparticles were added to growth media in individual and in combinations. Lead (50 mg L-1) was added to growth media. Thidiazuron and MgO nanoparticles increased plant growth, phenolic and flavonoid contents, free radical scavenging activity, and lead phytoaccumulation. The increase was highly significant in TDZ and MgO nanoparticle combination treatments (T5, T6). Treatment (T6) showed a sixfold increase in Pb accumulation (1721.73 ± 17.4 µg g-1 dry biomass) as compared to control (274.29 ± 4.23 µg-1g-1). Total phenolic and dry biomass showed significantly positive correlation in leaves (R2 = 0.73), stem (R2 = 0.58), and roots (R2 = 0.72). The correlation of Pb accumulation and phenolic contents was significantly positive in root (R2 = 0.80), stem (R2 = 0.92), and leaves (R2 = 0.69). Flavonoid showed a positive correlation with dry biomass and Pb accumulation. Antioxidant activity was highly increased in leaves followed by stem and root. Findings show that TDZ in combination with MgO nanoparticles can play a significant role in secondary metabolite production and Pb phytoaccumulation.


Assuntos
Antioxidantes/metabolismo , Chumbo/metabolismo , Óxido de Magnésio/farmacologia , Nanopartículas/química , Compostos de Fenilureia/farmacologia , Raphanus/efeitos dos fármacos , Poluentes do Solo/metabolismo , Tiadiazóis/farmacologia , Biodegradação Ambiental , Óxido de Magnésio/química , Compostos de Fenilureia/química , Componentes Aéreos da Planta/metabolismo , Raízes de Plantas/metabolismo , Raphanus/metabolismo , Tiadiazóis/química
7.
Chem Pharm Bull (Tokyo) ; 67(8): 888-895, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366838

RESUMO

New sugar hydrazones incorporating furan and/or 1,3,4-thiadiazole ring systems were synthesized by reaction of the corresponding hydrazide with different aldose sugars. Heterocyclization of the formed hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the heterocyclization process. The anticancer activity of the synthesized compounds was studied against human liver carcinoma cell (HepG-2) and at human normal retina pigmented epithelium cells (RPE-1). High activities were revealed by compounds 3, 12 and 14 with IC50 values near to that of the reference drug doxorubicin.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Furanos/farmacologia , Oxidiazóis/farmacologia , Açúcares/farmacologia , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/síntese química , Furanos/química , Células Hep G2 , Humanos , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade , Açúcares/síntese química , Açúcares/química , Tiadiazóis/síntese química , Tiadiazóis/química
8.
Mem Inst Oswaldo Cruz ; 114: e190017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271593

RESUMO

BACKGROUND: Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES: To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS: The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS: Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS: Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.


Assuntos
Nitroimidazóis/toxicidade , Tripanossomicidas/toxicidade , Células Sanguíneas/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa/métodos , Dano ao DNA , Humanos , Testes para Micronúcleos/métodos , Nifurtimox/química , Nifurtimox/toxicidade , Nitroimidazóis/química , Valores de Referência , Reprodutibilidade dos Testes , Tiadiazóis/química , Tiadiazóis/toxicidade , Fatores de Tempo , Tripanossomicidas/química , Trypanosoma cruzi/efeitos dos fármacos
9.
Int J Biol Macromol ; 135: 453-461, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150668

RESUMO

In this paper, a novel catalyst is introduced based on the introduction of an ionic liquid onto the ß-cyclodextrin. The ionic liquid-ß-cyclodextrin was anchored to magnetic starch (denoted ßCD-IL@M-Starch) and fully characterized by several methods including TEM, TGA, VSM and FT-IR. The catalyst was used for the synthesis of imidazo[2,1-b][1,3,4]thiadiazol-5-amine and imidazo[1,2-a]pyridin-3-amine derivatives. ßCD-IL@M-Starch catalyst showed very good activity in the synthesis of diphenylimidazo[2,1-b][1,3,4]thiadiazol-5-amine derivatives from the corresponding benzaldehyde, semicarbazide, benzaldehydes and isocyanides. The products were obtained in a mild reaction conditions in good isolated yields in the presence of ßCD-IL@M-Starch as catalyst. The catalyst showed to be magnetically reusable, and gave very good results in 10 sequential reactions.


Assuntos
Líquidos Iônicos/química , Imãs/química , Amido/química , Tiadiazóis/química , Tiadiazóis/síntese química , beta-Ciclodextrinas/química , Catálise , Técnicas de Química Sintética
10.
Carbohydr Res ; 480: 61-66, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176191

RESUMO

Herein we describe the synthesis of imidazo[2,1-b][1,3,4]thiadiazoles from carbohydrates with D-ribo and D-xylo configuration. The antiviral activity of these compounds was tested against Junín virus (the etiological agent of Argentine hemorrhagic fever). The p-chlorophenyl derivatives showed antiviral activity in a range of micromolar concentration.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Ribose/química , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Xilose/química , Antivirais/química , Técnicas de Química Sintética , Vírus Junin/efeitos dos fármacos , Tiadiazóis/química
11.
Molecules ; 24(13)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252614

RESUMO

The 1,3,4-thiadiazole derivatives (9a-i) were synthesized under solvent free conditions and their chemical composition was confirmed using different spectral tools (IR, Mass, and NMR spectrometry). All the synthesized compounds were screened for their anti-cancer potentiality over human breast carcinoma (MCF-7) and human lung carcinoma (A-549). Most of the tested compounds showed remarkable anti-breast cancer activity. However, compound 4 showed the most anti-lung cancer activity. Then, compounds with cytotoxic activity ≥ 80% over breast and lung cells were subjected to investigate their specificity on human normal skin cell line (BJ-1). Compounds 9b and 9g were chosen owing to their high breast anti-cancer efficacy and their safety, in order to study the possible anti-cancer mode of action. Otherwise, drug delivery provides a means to overcome the low solubility, un-targeted release, and limited bioavailability of the prepared 1,3,4-thiadiazole drug-like substances. Compounds 9b and 9g were chosen to be encapsulated in Na-alginate microspheres. The release profile and mechanism of both compounds were investigated, and the results revealed that the release profiles of both microspheres showed a sustained release, and the release mechanism was controlled by Fickian diffusion. Accordingly, these compounds are promising for their use in chemotherapy for cancer treatment, and their hydrophilicity was improved by polymer encapsulation to become more effective in their pharmaceutical application.


Assuntos
Antineoplásicos/farmacologia , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Células A549 , Antineoplásicos/química , Disponibilidade Biológica , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Microesferas , Estrutura Molecular , Solubilidade , Solventes , Relação Estrutura-Atividade , Tiadiazóis/química
12.
Mar Drugs ; 17(5)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083316

RESUMO

A deep study of the metabolic content of the tunicate Polycarpa aurata, collected from Indonesian coast, afforded the isolation of two novel alkaloids, polyaurines A (1) and B (2), along with two new p-substituted benzoyl derivatives (3 and 4) and four known compounds (5-8). The structural elucidation of the new secondary metabolites was assigned by 1D, 2D NMR, and HRESIMS techniques. Computational studies resulted a useful tool to unambiguously determine in polyaurine B the presence of rarely found 1,2,4-thiadiazole ring. The effects of polyaurines A and B on mammalian cells growth and on the viability of different blood-dwelling Schistosoma mansoni (phylum: Platyhelminthes) stages, as well as egg production, were evaluated. Both compounds resulted not cytotoxic; interestingly some of the eggs produced by polyaurine A-treated adult pairs in vitro are smaller, deformed, and/or fragmented; therefore, polyaurine A could represent an interesting bioactive natural molecule to be further investigated.


Assuntos
Schistosoma mansoni/efeitos dos fármacos , Tiadiazóis/química , Tiadiazóis/farmacologia , Urocordados/química , Alcaloides/química , Alcaloides/farmacologia , Animais , Indonésia , Concentração Inibidora 50 , Urocordados/metabolismo
13.
J Enzyme Inhib Med Chem ; 34(1): 955-972, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072147

RESUMO

In this article, a series of novel quinoline derivatives of ursolic acid (UA) bearing hydrazide, oxadiazole, or thiadiazole moieties were designed, synthesised, and screened for their in vitro antiproliferative activities against three cancer cell lines (MDA-MB-231, HeLa, and SMMC-7721). A number of compounds showed significant activity against at least one cell line. Among them, compound 4d exhibited the most potent activity against three cancer cell lines with IC50 values of 0.12 ± 0.01, 0.08 ± 0.01, and 0.34 ± 0.03 µM, respectively. In particular, compound 4d could induce the apoptosis of HeLa cells, arrest cell cycle at the G0/G1 phase, elevate intracellular reactive oxygen species level, and decrease mitochondrial membrane potential. In addition, compound 4d could significantly inhibit MEK1 kinase activity and impede Ras/Raf/MEK/ERK transduction pathway. Therefore, compound 4d may be a potential anticancer agent and a promising lead worthy of further investigation.


Assuntos
Antineoplásicos/farmacologia , MAP Quinase Quinase 1/antagonistas & inibidores , Oxidiazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Tiadiazóis/farmacologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , MAP Quinase Quinase 1/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Oxidiazóis/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinolinas/química , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tiadiazóis/química , Triterpenos/química
14.
Mol Cell ; 75(1): 53-65.e7, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31103421

RESUMO

The M2 muscarinic acetylcholine receptor (M2R) is a prototypical GPCR that plays important roles in regulating heart rate and CNS functions. Crystal structures provide snapshots of the M2R in inactive and active states, but the allosteric link between the ligand binding pocket and cytoplasmic surface remains poorly understood. Here we used solution NMR to examine the structure and dynamics of the M2R labeled with 13CH3-ε-methionine upon binding to various orthosteric and allosteric ligands having a range of efficacy for both G protein activation and arrestin recruitment. We observed ligand-specific changes in the NMR spectra of 13CH3-ε-methionine probes in the M2R extracellular domain, transmembrane core, and cytoplasmic surface, allowing us to correlate ligand structure with changes in receptor structure and dynamics. We show that the M2R has a complex energy landscape in which ligands with different efficacy profiles stabilize distinct receptor conformations.


Assuntos
Acetilcolina/química , Carbacol/química , Isoxazóis/química , Pilocarpina/química , Piridinas/química , Compostos de Amônio Quaternário/química , Receptor Muscarínico M2/química , Tiadiazóis/química , Acetilcolina/metabolismo , Animais , Baculoviridae/genética , Baculoviridae/metabolismo , Sítios de Ligação , Carbacol/metabolismo , Clonagem Molecular , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Isoxazóis/metabolismo , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Pilocarpina/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Piridinas/metabolismo , Compostos de Amônio Quaternário/metabolismo , Receptor Muscarínico M2/agonistas , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Células Sf9 , Spodoptera , Termodinâmica , Tiadiazóis/metabolismo
15.
Photochem Photobiol Sci ; 18(6): 1447-1460, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30957809

RESUMO

Fluorescence change systems that can respond to biological objects have attracted attention for use as biological probes and sensors. In this study, we report emission enhancement in a fluorescent aggregate composed of amphiphilic donor-acceptor dye molecules. The emission efficiency of the aggregate was reduced upon introducing a hydrophilic galactopyranose moiety, because of the decrease in the aggregate stability, which in turn was due to disruption of the hydrophilicity-hydrophobicity balance. In contrast, emission enhancement could be achieved by treatment with ß-galactosidase, as a result of the removal of the galactopyranose moiety. The change in aggregate stabilization based on the hydrophilicity-hydrophobicity balance leads to the emission enhancement into detectable ß-galactosidase activity.


Assuntos
Compostos de Anilina/química , Fluorescência , Corantes Fluorescentes/química , Tensoativos/química , Tiadiazóis/química , beta-Galactosidase/análise , Compostos de Anilina/síntese química , Corantes Fluorescentes/síntese química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Espectrometria de Fluorescência , Tensoativos/síntese química , Tiadiazóis/síntese química , beta-Galactosidase/metabolismo
16.
Molecules ; 24(6)2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30889918

RESUMO

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82⁻1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Desenho de Drogas , Simulação de Acoplamento Molecular , Tiadiazóis/química , Anti-Infecciosos/química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
17.
Mol Cell Biochem ; 458(1-2): 39-47, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30905023

RESUMO

The development of new antihyperlipidemic agents with higher potency and lower side effects is of high priority. In this study, 1,3,4 thiadiazole Schiff base derivatives were synthesized as potential peroxisome proliferation-activated receptor-α (PPARα) agonists and characterized using elemental analysis, FTIR, 1H-NMR, 13C-NMR and mass spectroscopy and then tested for their hypolipidemic activity in Triton WR-1339-induced acute hyperlipidemic rat model in comparison with bezafibrate. The compounds showed significant hypolipidemic activity. Induced fit docking showed that the compounds are potential activators of PPARα with binding scores - 8.00 Kcal/mol for 2,5-bis(4-hydroxybenzylidenamino)-1,3,4-thiadiazole. PCR array analysis showed an increase in the expression of several genes involved in lipid metabolism through mitochondrial fatty acid ß oxidation and are part of PPARα signaling pathway including Acsm3, Fabp4 and Hmgcs1. Gene expression of Lrp12 and Lrp1b involved in LDL uptake by liver cells and Cyp7a1 involved in cholesterol catabolism were also found to be upregulated.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes , PPAR alfa/agonistas , Tiadiazóis , Doença Aguda , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipolipemiantes/química , Hipolipemiantes/farmacocinética , Hipolipemiantes/farmacologia , Masculino , PPAR alfa/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tiadiazóis/química , Tiadiazóis/farmacocinética , Tiadiazóis/farmacologia
18.
J Sci Food Agric ; 99(9): 4331-4337, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30828813

RESUMO

BACKGROUND: Increasing numbers of fruit swelling agents have been used to improve the fruit rate and production yield of strawberries in recent years. The abuse of fruit swelling agents could lead to an increase in the deformation rate and abnormal coloration of strawberry and a decrease in quality at harvest. Therefore, understanding the harmful effects of fruit swelling agents on strawberry will provide guidance for their reasonable use. RESULTS: The residual determination method for measuring thidiazuron (TDZ) in strawberry was developed and validated by liquid chromatography and tandem mass spectrometry (LC-MS/MS). The recoveries of TDZ in strawberry were 97.9-108.5% with relative standard deviations of 0.9% to 5.3%. The dissipation rates of TDZ were different in strawberries cultivated under field and indoor conditions due to the differences in temperature and humidity. The ascorbic acid content increased when TDZ was applied at 2 mg kg-1 . The SOD (superoxide dismutase), POD (peroxidase) and CAT (catalase) activities of strawberry tended to decrease and subsequently increase following the application of TDZ, and the opposite changes occurred on the malondialdehyde (MDA) content of TDZ-treated strawberry. CONCLUSIONS: The analytical method for measuring TDZ in strawberry that was developed was suitable for dissipation studies on this compound. Antioxidant enzyme activities and the MDA content of strawberry were altered, and some reverse effects, such as membrane damage, were inhibited when TDZ was applied. The data obtained in this study might provide suggestions to reduce the adverse effects of TDZ on strawberry and may help to guide the safe and proper use of TDZ in strawberry. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/análise , Fragaria/efeitos dos fármacos , Malondialdeído/análise , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacologia , Reguladores de Crescimento de Planta/química , Reguladores de Crescimento de Planta/farmacologia , Tiadiazóis/química , Tiadiazóis/farmacologia , Antioxidantes/metabolismo , Catalase/análise , Catalase/metabolismo , Cromatografia Líquida , Citocininas/química , Citocininas/farmacologia , Fragaria/química , Fragaria/enzimologia , Frutas/química , Frutas/efeitos dos fármacos , Frutas/enzimologia , Malondialdeído/metabolismo , Peroxidases/análise , Peroxidases/metabolismo , Proteínas de Plantas/análise , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Espectrometria de Massas em Tandem
19.
Molecules ; 24(5)2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30823444

RESUMO

A small library of new drug-1,3,4-thiazidazole hybrid compounds (3a⁻3i) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound 3b (IC50 18.1 ± 0.9 nM), which was the most promising molecule in the series, and was substantially more active than the reference drug (neostigmine methyl sulfate; IC50 2186.5 ± 98.0 nM). Kinetic studies were performed to elucidate the mode of inhibition of the enzyme, and the compounds showed mixed-type mechanisms for inhibiting AChE. The Ki of 3b (0.0031 µM) indicates that it can be very effective, even at low concentrations. Compounds 3a⁻3i all complied with Lipinski's Rule of Five, and showed high drug-likeness scores. The pharmacokinetic parameters revealed notable lead-like properties with insignificant liver and skin-penetrating effects. The structure⁻activity relationship (SAR) analysis indicated π⁻π interactions with key amino acid residues related to Tyr124, Trp286, and Tyr341.


Assuntos
Acetilcolinesterase/química , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Tiadiazóis/química , Relação Estrutura-Atividade
20.
Macromol Rapid Commun ; 40(8): e1900005, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30779392

RESUMO

Various molecular weight π-conjugated donor-acceptor polymers based on thiadiazole and thiophene units are investigated with respect to nanoscale film morphology and digital memory performance. Interestingly, all polymers reveal excellent n-type digital permanent memory characteristics, which are governed by the combination of Ohmic and trap-limited space charge limited conductions via a hopping process using thiadiazole and thiophene units as charge traps and stepping stones. The digital memory performance is significantly influenced by the film morphology details that vary with the polymer molecular weight as well as the film thickness. A higher population of face-on structure formation, as well as higher molecular weight, provides a wider film thickness window of digital memory operation. Overall, π-conjugated PBTDzTV polymers are suitable for the production of high-performance, programmable n-type permanent memory devices with very low power consumption.


Assuntos
Nanopartículas/química , Polímeros/química , Tiadiazóis/química , Tiofenos/química , Estrutura Molecular , Peso Molecular
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