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1.
J Mol Graph Model ; 100: 107690, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32745925

RESUMO

Coronavirus epidemic 2019 (COVID-19), caused by novel coronavirus (2019-nCoV), is newly increasing worldwide and elevating global health concerns. Similar to SARS-CoV and MERS-CoV, the viral key 3-chymotrypsin-like cysteine protease enzyme (3CLPro), which controls 2019-nCoV duplications and manages its life cycle, could be pointed as a drug discovery target. Herein, we theoretically studied the binding ability of 10 structurally different anthocyanins with the catalytic dyad residues of 3CLpro of 2019-nCoV using molecular docking modelling. The results revealed that the polyacylated anthocyanins, including phacelianin, gentiodelphin, cyanodelphin, and tecophilin, were found to authentically bind with the receptor binding site and catalytic dyad (Cys145 and His41) of 2019-nCoV-3CLpro. Our analyses revealed that the top four hits might serve as potential anti-2019-nCoV leading molecules for further optimization and drug development process to combat COVID-19. This study unleashed that anthocyanins with specific structure could be used as effective anti-COVID-19 natural components.


Assuntos
Antocianinas/química , Antivirais/química , Benzopiranos/química , Betacoronavirus/química , Cisteína Endopeptidases/química , Glucosídeos/química , Inibidores de Proteases/química , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Betacoronavirus/enzimologia , Sítios de Ligação , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Alinhamento de Sequência , Relação Estrutura-Atividade , Termodinâmica , Proteínas não Estruturais Virais/antagonistas & inibidores
2.
Nat Commun ; 11(1): 793, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034152

RESUMO

Fluorescence-based technologies have revolutionized in vivo monitoring of biomolecules. However, significant technical hurdles in both probe chemistry and complex cellular environments have limited the accuracy of quantifying these biomolecules. Herein, we report a generalizable engineering strategy for dual-emission anti-Kasha-active fluorophores, which combine an integrated fluorescein with chromene (IFC) building block with donor-π-acceptor structural modification. These fluorophores exhibit an invariant near-infrared Kasha emission from the S1 state, while their anti-Kasha emission from the S2 state at around 520 nm can be finely regulated via a spirolactone open/closed switch. We introduce bio-recognition moieties to IFC structures, and demonstrate ratiometric quantification of cysteine and glutathione in living cells and animals, using the ratio (S2/S1) with the S1 emission as a reliable internal reference signal. This de novo strategy of tuning anti-Kasha-active properties expands the in vivo ratiometric quantification toolbox for highly accurate analysis in both basic life science research and clinical applications.


Assuntos
Bioquímica/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Células A549 , Animais , Benzopiranos/química , Cisteína/análise , Feminino , Fluoresceína/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Glutationa/análise , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Piranos/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espironolactona/química
3.
Chemosphere ; 248: 125992, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006832

RESUMO

Natural colloids can influence the binding mechanisms between nano-hydroxyapatite (nHAP) and Cd(II). In this study, the effects of organic and inorganic natural colloids on Cd(II) sorption onto nHAP were compared. Different experimental approaches combined with the additivity model and the Extended-Derjaguin-Landau-Verwey-Overbeek model were used to quantify the distribution of Cd(II) in the systems of nHAP and natural colloid, and the interaction energy between particles. The results showed that both fulvic acid (FA) and montmorillonite colloid (MONT) had the promotion and inhibition effects on Cd(II) sorption onto nHAP. Coexistence of FA or MONT could stabilize nHAP particles. FA could adsorb onto nHAP particle surface via carboxylic and phenolic groups, which increased nHAP electronegativity and formed steric resistance effect. Coexistence of MONT mainly increased nHAP electronegativity. These effects prevented the reduction of the specific surface area of nHAP particles and increased the Cd(II) sorption onto nHAP. However, the inhibition effect on Cd(II) sorption was enhanced with increasing concentration of FA or MONT because more soluble FA-Cd or suspended MONT-Cd complexes formed in the system. In nHAP-FA-Cd systems, the Cd(II) sorption onto FA was well predicted but that onto solid phase was underestimated by the additivity model. In nHAP-MONT-Cd systems, Cd(II) sorbed onto mixtures of nHAP and MONT was well described by the additive model. The findings of this study can help to understand the fate of Cd(II) in natural water and soil.


Assuntos
Bentonita/química , Benzopiranos/química , Cádmio/química , Modelos Químicos , Poluentes do Solo/química , Adsorção , Cádmio/metabolismo , Coloides/química , Durapatita/química , Solo/química , Poluentes do Solo/análise , Água
4.
Carbohydr Polym ; 230: 115603, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887950

RESUMO

Invisible high-security anticounterfeiting inks were developed by surface-modification of functionalized latex nanoparticles with spiropyran derivatives, which display both photochromism and fluorescence upon UV irradiation at the same time. The functionalized latex nanoparticles show different spherical, doughnut-like, and red blood cell-like morphologies depending on concentration and type of its functional groups. Microscopic investigation of the impregnated cellulosic papers with latex nanoparticles display that epoxy-functionalized spherical latex nanoparticles have considerable packing and stability on the surface of the cellulosic substrate by formation of hydrogen bonding. Epoxy-functionalized latex nanoparticles containing spiropyran were used for preparation of high-security photochromic/fluorescent anticounterfeiting inks for print-marking of different cellulosic security documents such as certificate, money, and passport with different marks. The printed marks and finger-prints on the cellulosic security documents display photochromism and red fluorescence emission upon UV irradiation with high intensity and brightness.


Assuntos
Celulose/química , Nanopartículas/química , Papel/normas , Impressão/métodos , Polímeros Responsivos a Estímulos/química , Benzopiranos/química , Fluorescência , Ligação de Hidrogênio , Indóis/química , Tinta , Látex/química , Nitrocompostos/química
5.
Chemosphere ; 243: 125413, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31765900

RESUMO

Naturally silver nanoparticles (AgNPs) have been widely observed in ore deposits, coal, natural water and soil environment. Identifying the source of these naturally AgNPs could be helpful for the elucidation of the geochemical cycle of Ag+ and AgNPs. This paper presents the formation of AgNPs by reducing Ag+ in the presence of soil organic matter (SOM) under various environmentally relevant conditions. The formation of AgNPs associated with various SOM (peat humic acid (PHA), peat fulvic acid (PFA), and commercial humic acids (HA-1 and HA-2)) was determined and compared. The physicochemical properties of the tested SOM were studied by electron paramagnetic resonance (EPR) and attenuated total reflection-infrared (ATR-FTIR) techniques. The formation of AgNPs depended on reductive reactions mediated by SOM. Other influential parameters that influenced the formation of AgNPs included concentrations of Ag+ and SOM and the reaction temperature on AgNPs. The produced AgNPs were characterized by transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The mean hydrodynamic diameters of AgNPs associated with PHA and PFA were in range from 2.5 to 15 nm, which were smaller than that produced from HA-1 and HA-2 in the range from 20 to 120 nm. Two different Ag states, i.e., Ag2O and Ag0 species, were observed by XPS technique. The results indicated that the formation of AgNPs depends largely on the types and the properties of natural organic matter. These findings have important implications for the fate of AgNPs under the soil environment.


Assuntos
Nanopartículas Metálicas/química , Prata/química , Solo/química , Benzopiranos/química , Substâncias Húmicas , Microscopia Eletrônica de Transmissão , Temperatura
6.
Phytochemistry ; 170: 112224, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812919

RESUMO

Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ8(12) double bond on γ-lactone ring and the presence of CH3-2' in fatty chains may increase their inhibitory activity.


Assuntos
Aspergillus/química , Benzopiranos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Pigmentos Biológicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Benzopiranos/química , Benzopiranos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
7.
Chemosphere ; 242: 125256, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31704524

RESUMO

Ultraviolet-quenching substances (UVQS), recently identified pollutants in landfill leachate, can interfere with ultraviolet disinfection when landfill leachate is co-treated with municipal sewage. This study investigated the elimination of UVQS in mature landfill leachates through a membrane bioreactor (MBR) and a semi-aerobic aged refuse biofilter (SAARB). Humus (i.e., fulvic and humic acids) was the main component of organic matter in both MBR- and SAARB-treated landfill leachates, while there was a more stable chemical structure of humus in the MBR-treated leachate. The concentration of UVQS in MBR-treated mature landfill leachate was higher than that of SAARB-treated leachate. Ozonation can degrade UVQS effectively, especially for landfill leachate containing a high concentration UVQS (i.e., MBR-treated landfill leachate). However, a large accumulation of small molecule acid might be caused by ozonation for highly concentrated UVQS in landfill leachate, leading to the delayed degradation of total organic carbon. Moreover, ozonation degraded both fulvic acid and humic acid; and degraded humic acid more effectively. For instance, 88.0% removal (MBR-CP2) and 96.0% removal (SAARB-CP2) of humic acid was higher than those (83.3% for MBR-CP1 and 92.3% for SAARB-CP1) of fulvic acid. The destruction of UV-quenching functional groups of organics (such as CC) by ozone was the main UVQS degradation mechanism of ozonation applied to MBR- and SAARB-treated landfill leachates. Therefore, the ozonation process can efficiently decrease UV absorption intensity in both MBR- and SAARB-treated landfill leachates.


Assuntos
Reatores Biológicos , Filtração , Ozônio/química , Poluentes Químicos da Água/química , Benzopiranos/química , Resíduos de Alimentos , Substâncias Húmicas/análise , Eliminação de Resíduos , Esgotos , Raios Ultravioleta , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos da radiação
8.
Chem Biol Interact ; 316: 108924, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31843629

RESUMO

Parameritannin A-2 (PA-2) is a natural product extracted from the stems of the plant Urceola huaitingii. Our previous studies have shown that PA-2 exhibits significant synergistic anticancer effects with doxorubicin (DOX) in HGC27 gastric cancer cell lines. Here we report that our isobolographic analysis confirms the synergistic cytotoxic effects of PA-2 and DOX in HGC27 cells. Flow cytometry and immunoblotting indicate that PA-2 enhances DOX-mediated apoptosis. Importantly, PA-2 enhances the intracellular accumulation of DOX in HGC27 cells. The combination of DOX and PA-2 remarkably increases the release of cytochrome C and the activation of caspase-3 and caspase-9, compared with DOX treatment alone. Moreover, PA-2 attenuates the DOX-induced activation of Akt, ERK1/2 and p38 signaling pathways, providing a molecular mechanism for the synergistic effects of DOX and PA-2 in the induction of apoptosis. In conclusion, our studies demonstrate that PA-2 and DOX synergistically induce mitochondria-dependent apoptosis as PA-2 inhibits the PI3K/Akt, ERK1/2 and p38 pathways in HGC27 cells. These findings suggest that the combination treatment with PA-2 and DOX may represent a potent therapy for gastric cancer.


Assuntos
Apocynaceae/química , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Mitocôndrias/metabolismo , Naftalenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apocynaceae/metabolismo , Benzopiranos/química , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Humanos , Mitocôndrias/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Naftalenos/química , Fosfatidilinositol 3-Quinases/metabolismo , Caules de Planta/química , Caules de Planta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Eur J Med Chem ; 185: 111785, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669851

RESUMO

Multi-target-directed ligands seem to be an interesting approach to the treatment of complex disorders such as Alzheimer's disease. The aim of the present study was to find novel multifunctional compounds in a non-imidazole histamine H3 receptor ligand library. Docking-based virtual screening was applied for selection of twenty-six hits which were subsequently evaluated in Ellman's assay for the inhibitory potency toward acetyl- (AChE) and butyrylcholinesterase (BuChE). The virtual screening with high success ratio enabled to choose multi-target-directed ligands. Based on docking results, all selected ligands were able to bind both catalytic and peripheral sites of AChE and BuChE. The most promising derivatives combined the flavone moiety via a six carbon atom linker with a heterocyclic moiety, such as azepane, piperidine or 3-methylpiperidine. They showed the highest inhibitory activities toward cholinesterases as well as well-balanced potencies against H3R and both enzymes. Two derivatives were chosen - 5 (IC50 = 0.46 µM (AChE); 0.44 µM (BuChE); Ki = 159.8 nM (H3R)) and 17 (IC50 = 0.50 µM (AChE); 0.76 µM (BuChE); Ki = 228.2 nM (H3R)), and their inhibition mechanism was evaluated in kinetic studies. Both compounds displayed non-competitive mode of AChE and BuChE inhibition. Compounds 5 and 17 might serve as good lead structures for further optimization and development of novel multi-target anti-Alzheimer's agents.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Antagonistas dos Receptores Histamínicos H3/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptores Histamínicos H3/metabolismo , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Animais , Benzopiranos/síntese química , Benzopiranos/química , Benzopiranos/farmacologia , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Electrophorus , Antagonistas dos Receptores Histamínicos H3/síntese química , Antagonistas dos Receptores Histamínicos H3/química , Cavalos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Piperidinas/síntese química , Piperidinas/química , Piperidinas/farmacologia , Relação Estrutura-Atividade
10.
Mini Rev Med Chem ; 19(20): 1717-1725, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31880237

RESUMO

BACKGROUND & OBJECTIVE: A new series of thiazoles substituted on the chromene scaffold were prepared by facial approaches starting from (E)-1-(2,3-Dihydrochromen-4-ylidene)thiosemicarbazide derivatives (2a,b). The thiosemicarbazides (2a,b) were reacted with a series of α-halo carbonyl compounds to give the corresponding rhodanine analogues and reacted also with C-acetyl-or Cethoxy- N-hydrazonoyl chlorides to afford the corresponding tri- and tetra-substituted hybrid hydrazinyl thiazole substituted chromenes. METHODS: The newly synthesized compounds were screened for their in vitro antimicrobial and antitumor activities by agar diffusion method and MTT assay, respectively. RESULTS: The results of the antimicrobial activity revealed that some of the new compounds exhibited excellent activity against pathogenic microorganism; Candida albicans compared with Ciprofloxacin and nystatin, as the reference drugs. All of the tested compounds exhibited significant cytotoxic activities comparable to that of the reference drug; Doxorubicin® (on HCT116 (colorectal carcinoma human cell line).


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Ágar/química , Antibacterianos/química , Antineoplásicos/química , Bacillus subtilis/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Difusão , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Células HCT116 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/síntese química
11.
Nutrients ; 12(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861646

RESUMO

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated ß-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of ß-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3ß, thereby preventing ß-catenin from degradation. Additionally, si-ß-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of ß-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.


Assuntos
Adipogenia/efeitos dos fármacos , Benzopiranos/farmacologia , Butiratos/farmacologia , Gordura Intra-Abdominal/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , beta Catenina/metabolismo , Benzopiranos/química , Biomarcadores/metabolismo , Butiratos/química , Células Cultivadas , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Estrutura Molecular , Transdução de Sinais , Regulação para Cima
12.
J Agric Food Chem ; 67(47): 13040-13050, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31670962

RESUMO

Two new natural 10-membered macrolides (1, 2) and one chromene-4,5-dione derivative (3), named stagonolides J and K and stagochromene A, respectively, were isolated from the phytopathogenic fungus Stagonospora cirsii S-47, together with two known compounds, stagonolide A (4) and herbarumin I (5). Stagonolides J and K and stagochromene A were characterized as (5E,7R*,8S*,9R*)-7,8-dihydroxy-9-propyl-5-nonen-9-olide, (5E,7R,9S)-7-hydroxy-9-propyl-5-nonen-9-olide, and (2R*,3R*)-3-hydroxy-2-propyltetrahydro-2H-chromene-4,5(3H,4aH)-dione, respectively, by spectroscopic (mostly by NMR and ESIMS) data. Compounds 1-5 showed different rates of phytotoxic activity on punctured leaf discs of Sonchus arvensis. The antimicrobial, cytotoxic, and antiprotozoal activity of isolated compounds was also evaluated. Based on our data, stagonolide K and herbarumin I can be proposed as a potential scaffold for the development of a new natural herbicide and estimated as possible selection/quality markers of a bioherbicide based on S. cirsii, while stagonolide A can be considered as a mycotoxin.


Assuntos
Ascomicetos/química , Benzopiranos/química , Herbicidas/química , Compostos Heterocíclicos com 1 Anel/química , Lactonas/química , Macrolídeos/química , Sonchus/efeitos dos fármacos , Benzopiranos/farmacologia , Herbicidas/farmacologia , Compostos Heterocíclicos com 1 Anel/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , Estrutura Molecular , Micotoxinas/química , Micotoxinas/farmacologia , Sonchus/crescimento & desenvolvimento
13.
Chem Commun (Camb) ; 55(98): 14840-14843, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31768510

RESUMO

XimA is a unique amide synthetase that belongs to the ANL superfamily of adenylating enzymes, but with a special structural fold. In order to improve the enzyme promiscuity, we engineered XimA by site-directed mutagenesis at a specific position based on our theoretical model of XimA. Thus, we were able to produce diverse benzopyran derivatives with up to 15 different l-form and d-form amino acid substitutions, catalyzed by several XimA variants. Molecular docking and molecular dynamics simulations conducted for various XimA systems provide further structural insights into the substitution effects of the phenylalanine-201 as an active site residue on protein dynamics and enzyme catalysis.


Assuntos
Amida Sintases/metabolismo , Treonina/análogos & derivados , Amida Sintases/genética , Benzopiranos/química , Benzopiranos/metabolismo , Cinética , Mutagênese Sítio-Dirigida , Peptídeo Sintases/metabolismo , Engenharia de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Streptomyces/química , Streptomyces/metabolismo , Especificidade por Substrato , Treonina/biossíntese , Treonina/química
14.
Biomater Sci ; 7(12): 4944-4962, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31650136

RESUMO

Oligonucleotides are widely used biological materials in the fields of biomedicine, nanotechnology, and materials science. Due to the demands for the photoregulation of DNA activities, scientists are placing more and more research interest in the interactions between reversible photochromic molecules and DNAs. Photochromic molecules can work as switches for regulating the DNAs' behavior under light irradiation; meanwhile, DNAs also exert influence over the photochromic molecules. The photochromic molecules can be attached to DNAs either by covalent bonds or by noncovalent forces, which results in different regulative functions. Azobenzenes, spiropyrans, diarylethenes, and stilbene-like compounds are important photochromic molecules working as photoswitches. By summarizing their interactions with oligonucleotides, this review intends to facilitate the relevant research on oligonucleotides/photochromic molecules in the biological and medicinal fields and in materials science.


Assuntos
Substâncias Luminescentes/química , Oligonucleotídeos/química , Compostos Azo/química , Benzopiranos/química , Indóis/química , Estrutura Molecular , Nitrocompostos/química
15.
Planta Med ; 85(16): 1233-1241, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31610603

RESUMO

The chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-ß-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-ß-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-ß-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i. p. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i. v., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i. p. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-ß-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , Benzopiranos/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Animais , Benzopiranos/química , Benzopiranos/farmacocinética , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Ratos , Solubilidade
16.
J Agric Food Chem ; 67(42): 11769-11777, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31575115

RESUMO

The inhibitory effect of brazilin against α-synuclein (α-syn) fibrillogenesis, disruption effect against mature fibrils, and the following cytotoxicity were examined by systematical biochemical, biophysical, cellular biological, and molecular simulation experiments. It is found that brazilin inhibited α-syn fibrillogenesis and disrupted the performed fibrils with a concentration-dependent manner. Moreover, cellular experimental data showed that brazilin effectively reduced the cytotoxicity induced by α-syn aggregates. Finally, molecular dynamics simulations were performed to explore the interactions between brazilin and α-syn pentamer. It is found that brazilin directly interacts with α-syn pentamer, and the hydrophobic interactions are favorable for brazilin binding with the α-syn pentamer, while the electrostatic part provides adverse effects. Three binding regions were identified to inhibit α-syn fibrillogenesis or disrupt the preformed aggregates. Furthermore, six important residues (i.e., G51, V52, A53, E61, V66, and K80) of α-syn were also identified. We expected that brazilin is an effective agent against α-syn fibrillogenesis and associated cytotoxicity.


Assuntos
Amiloide/química , Benzopiranos/química , Substâncias Protetoras/química , alfa-Sinucleína/química , Motivos de Aminoácidos , Amiloide/metabolismo , Amiloide/toxicidade , Animais , Benzopiranos/metabolismo , Linhagem Celular , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Células PC12 , Agregados Proteicos , Ligação Proteica , Ratos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/toxicidade
17.
ACS Appl Mater Interfaces ; 11(41): 38226-38231, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529963

RESUMO

Near-infrared (NIR) microlasers play a significant role in telecommunication and biomedical tissue imaging. However, it remains a big challenge to realize NIR microlasers because of the difficulty in preparing highly efficient NIR luminescent materials and perfect optical resonators. Here, we propose a molecular design strategy to creatively realize the first spiropyrane (SP)-based NIR microlasers with low threshold from self-assembled microsphercial caps. The tetraphenylethylene (TPE) moiety with a highly twisted conformation provides a large free volume to facilitate the photoisomerization process of SP and enhance NIR emission of merocyanine in the solid state. Moreover, self-assembled TPE-SP microsphercial caps simultaneously serve as gain media and resonant microcavities, providing optical gain and feedback for NIR laser oscillations with a low threshold (3.68 µJ/cm2). These results are beneficial for deeply understanding the SP microstructures-lasing emission characteristic relationship and provide a useful guideline for the rational molecular design of NIR microlasers with special functionalities.


Assuntos
Benzopiranos/química , Indóis/química , Lasers , Microesferas , Nitrocompostos/química
18.
Adv Mater ; 31(44): e1904799, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31523871

RESUMO

Nonlinear optical microscopy has become a powerful tool in bioimaging research due to its unique capabilities of deep optical sectioning, high-spatial-resolution imaging, and 3D reconstruction of biological specimens. Developing organic fluorescent probes with strong nonlinear optical effects, in particular third-harmonic generation (THG), is promising for exploiting nonlinear microscopic imaging for biomedical applications. Herein, a simple method for preparing organic nanocrystals based on an aggregation-induced emission (AIE) luminogen (DCCN) with bright near-infrared emission is successfully demonstrated. Aggregation-induced nonlinear optical effects, including two-photon fluorescence (2PF), three-photon fluorescence (3PF), and THG, of DCCN are observed in nanoparticles, especially for crystalline nanoparticles. The nanocrystals of DCCN are successfully applied for 2PF microscopy at 1040 nm NIR-II excitation and THG microscopy at 1560 nm NIR-II excitation, respectively, to reconstruct the 3D vasculature of the mouse cerebral vasculature. Impressively, the THG microscopy provides much higher spatial resolution and brightness than the 2PF microscopy and can visualize small vessels with diameters of ≈2.7 µm at the deepest depth of 800 µm in a mouse brain. Thus, this is expected to inspire new insights into the development of advanced AIE materials with multiple nonlinearity, in particular THG, for multimodal nonlinear optical microscopy.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Pontos Quânticos/química , Animais , Benzopiranos/química , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Carbazóis/química , Teoria da Densidade Funcional , Feminino , Humanos , Camundongos Endogâmicos ICR , Nanopartículas , Nitrilos/química , Espectroscopia de Luz Próxima ao Infravermelho
19.
Int J Biol Macromol ; 140: 605-613, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437499

RESUMO

A library of known and new 4-aroyl-pyrano[3,2-c]chromenes have been synthesized through the one-pot, three-component reaction of 4-hydroxycoumarin, aryl glyoxals, and malononitrile or ethyl cyanoacetate in the presence of sodium alginate without any post modification, as a biopolymeric bifunctional organocatalyst, in EtOH under reflux conditions in short times. The desired products were obtained in high to excellent yields under optimized conditions. This procedure offers many advantages, such as operational simplicity, a green solvent system, short reaction times, high to excellent yields, simple work up and separation, and using a natural commercially available polysaccharide that is transition-metal-free, biodegradable and recoverable. Furthermore, sodium alginate can be recycled at least four times with negligible loss of its catalytic activity.


Assuntos
Alginatos/química , Benzopiranos/química , 4-Hidroxicumarinas/química , Acetatos/química , Catálise , Química Verde/métodos
20.
Int J Biol Macromol ; 139: 181-190, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369784

RESUMO

Fulvic acid (FA) was modified with p-phenylenediamine via iodine and triphenylphosphine as catalyst. The microstructure characterization for modified fulvic acid (MFA) were investigated by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively, which demonstrated that MFA was characteristic of amide derivative. Moreover, poly(lactic acid) (PLA)/MFA composites was prepared with MFA as filler by melt blending. The mechanical tests showed that the impact strength of PLA/(0.5wt%) MFA composites were increased by 97.2%. Scanning electron microscopy demonstrated that the impact fracture of PLA/(0.5wt%) MFA composites were characteristic ductile fracture. The rheological behavior analysis showed that PLA had good interfacial compatibility with MFA. The crystallinity of PLA was increased from 4.9% to 36.9% with the introduction of MFA. The polarized optical microscopy presented that the crystallization nucleation rate of PLA were rapidly increased, which resulted in the increased comprehensive performance of PLA. The results of enzymatic degradation mechanism showed that MFA increased the Km of proteinase K, and had some inhibition to the degradation of PLA, but PLA still remained degraded evidently.


Assuntos
Benzopiranos/química , Endopeptidase K/metabolismo , Poliésteres/química , Poliésteres/metabolismo , Reologia , Cristalização , Cinética , Resistência à Tração
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