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1.
Biomed Chromatogr ; 34(2): e4757, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31755125

RESUMO

Er-Zhi-Wan (EZW) is a traditional Chinese medicine with many clinical applications and used as a health product in East Asia. Five active ingredients (salidroside, specnuezhenide, nuezhenoside, luteolin, and oleanolic acid) were screened out from EZW to develop an in vitro rapid evaluation method for the classification of in vivo drug absorption behavior by biopharmaceutics classification system (BCS). Ultra-performance liquid chromatography was used for quantitative analysis. Solubility and permeability were assayed by equilibrium solubility and multiple models: everted rat intestinal sac model, cultured Caco-2 cells, octanol-water partition coefficient (LogP) method. The BCS properties of drugs were predicted using software applications, and the correlations of measured and predicted values of factors affecting oral drug absorption were calculated. The results were verified by measuring the absolute bioavailability of the active ingredients. Salidroside, specnuezhenide, and nuezhenoside were classified as BCS class III drugs, and luteolin was classified as a BCS class III/I drug because of the difference in LogP and intestinal permeability. Oleanolic acid was classified as a BCS class II/IV drug in acidic media and BCS class I/III drug in other media. Overall, EZW may be classified as a BCS class III drug, and permeability was identified as the primary factor limiting absorption. The results provide a novel method for the evaluation of the in vivo absorption of oral traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Disponibilidade Biológica , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Glucosídeos/sangue , Glucosídeos/química , Glucosídeos/farmacocinética , Humanos , Absorção Intestinal/fisiologia , Limite de Detecção , Modelos Lineares , Luteolina/sangue , Luteolina/química , Luteolina/farmacocinética , Masculino , Ácido Oleanólico/sangue , Ácido Oleanólico/química , Ácido Oleanólico/farmacocinética , Permeabilidade , Fenóis/sangue , Fenóis/química , Fenóis/farmacocinética , Piranos/sangue , Piranos/química , Piranos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Software , Solubilidade
2.
J Agric Food Chem ; 67(45): 12558-12564, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31609622

RESUMO

All four stereoisomers of naturally occurring 6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (1) were synthesized by employing yeast-reduction products with high optical purity [from 95% enantiomeric excess (ee) to more than 99% ee], and then their phytotoxicities against lettuce and Italian ryegrass were evaluated. In the Italian ryegrass seedlings test, (6S,2'R)-1 showed the most potent and stereospecific activity against the shoots (IC50 = 260 µM) and roots (IC50 = 43.2 µM), with a significant difference from other stereoisomers. The highest seed germination inhibitory activity against Italian ryegrass seed was also observed in (6S,2'R)-1, showing a 53% germination ratio from the control at 1000 µM. This advantageous (6S,2'R) stereochemistry was employed in the syntheses of α,ß-dihydro, 2'-dehydroxy, and 2'-methoxy derivatives 13-15. By the test using these derivatives, the importance of the α,ß-unsaturated double bond and hydroxy group bonding to a chiral center on the 6-alkyl chain of 5,6-dihydro-α-pyrone for phytotoxicity was determined. In the test against lettuce, the 6S configuration and (6S,2'S) configuration were necessary for growth inhibition (IC50 = ca. 60 µM) and germination inhibition (63% germination ratio at 1000 µM), respectively.


Assuntos
Carbono/química , Herbicidas/farmacologia , Piranos/química , Carbono/farmacologia , Germinação/efeitos dos fármacos , Herbicidas/síntese química , Herbicidas/química , Alface/efeitos dos fármacos , Alface/crescimento & desenvolvimento , Lolium/efeitos dos fármacos , Lolium/crescimento & desenvolvimento , Estrutura Molecular , Piranos/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
3.
Org Biomol Chem ; 17(37): 8571-8588, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31517368

RESUMO

Ketoreductase from growing cells of Klebsiella pneumoniae (NBRC 3319) acts as an efficient reagent for converting racemic α-benzyl/cinnamyl substituted-ß-ketoesters to the corresponding ß-hydroxy esters with excellent yields and stereoselectivities (ee and de >99 %). The reactions described herein followed a biocatalytic dynamic kinetic reductive resolution (DKRR) pathway, which is reported for the first time with such substrates. It was found that the enzyme system can accept substituted mono-aryl rings with different electronic natures. In addition, it also accepts a substituted naphthyl ring and heteroaryl ring in the α-position of the parent ß-ketoester. The synthesized enantiopure ß-hydroxy esters were then synthetically manipulated to valuable tetrahydropyran building blocks.


Assuntos
Klebsiella pneumoniae/enzimologia , Oxirredutases/metabolismo , Piranos/metabolismo , Termodinâmica , Biocatálise , Cinética , Estrutura Molecular , Oxirredução , Piranos/química
4.
Chem Pharm Bull (Tokyo) ; 67(9): 953-958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474735

RESUMO

Asymmetric total syntheses of dihydropyran containing natural products, (+)-eurotiumide F and (+)-eurotiumide G have been described. These total syntheses revealed the absolute configuration of eurotiumide F and G, and confirmed the reported structure of eurotiumide F and revised the reported structure of eurotiumide G. Highlight of these syntheses is thermal rearrangement with 4-methoxyisochroman-1-one derivative having propargyl ether on phenolic ether under thermal condition to construct dihydropyran ring. X-Ray crystallographic analysis of (+)-eurotiumide G clarified the stereochemistry at the C1-position.


Assuntos
Produtos Biológicos/química , Piranos/química , Produtos Biológicos/síntese química , Cristalografia por Raios X , Conformação Molecular , Piranos/síntese química , Solventes/química , Estereoisomerismo
5.
Talanta ; 205: 120125, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450407

RESUMO

The precise detection of endogenous biothiols such as Glutathione (GSH), Cysteine (Cys) and Homocysteine (HCy) is a long-standing human health concern. A dual-channel fluorescent probe (Cy-DC) composed of two fluorescence reporting units (dicyanomethylene-4H-pyran and cyanine) with ether linker for distinguishing different endogenous biothiols was designed and synthesized. Due to the two well-resolved emission bands, this probe possesses an outstanding capability for selectively sensing of endogenous GSH spatiotemporally and synchronously. Nevertheless, in the near infrared (NIR) channel (λex = 700 nm, λem = 810 nm), the probe can produce strong fluorescence only when it responds to GSH. Besides, the cells (L02 and U87) imaging, it also demonstrated that Cy-DC could successfully discriminate between GSH and Cys/Hcy with high sensitivity with the limit of detection (LOD) is 24 nM and 32 nM (3*SD/K). Particularly, the probe was applied in detecting solid tumor by the naked-eye and NIR imaging successfully, which revealed that the probe has promising prospects in clinical diagnosis applications.


Assuntos
Corantes Fluorescentes/química , Glutationa/metabolismo , Raios Infravermelhos , Mitocôndrias/metabolismo , Compostos de Sulfidrila/química , Animais , Carbocianinas/química , Linhagem Celular Tumoral , Sobrevivência Celular , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacocinética , Humanos , Limite de Detecção , Camundongos , Piranos/química , Espectrometria de Fluorescência , Distribuição Tecidual
6.
Molecules ; 24(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405075

RESUMO

In this review, we discuss the nature of the different physicochemical factors affecting the valence isomerism between 2H-pyrans (2HPs) and 1-oxatrienes, and we describe the most versatile synthetic methods reported in recent literature to access to 2HPs, with the only exception of 2HPs fused to aromatic rings (i.e., 2H-chromenes), which are not included in this review.


Assuntos
Piranos/química , Piranos/síntese química , Catálise , Estereoisomerismo
7.
Talanta ; 205: 120107, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450415

RESUMO

A comprehensive structural characterization of the complex family of isomeric forms related to Oleuropein aglycone (OA) detected in virgin olive oil (VOO) was performed by reverse phase liquid chromatography with electrospray ionization and Fourier-transform mass spectrometry (RPLC-ESI-FTMS), integrated by enzymatic/chemical reactions performed on Oleuropein, the natural precursor of OA. First, some of the OA-related isomers typically observed in VOO extracts were generated upon enzymatic hydrolysis of the glycosidic linkage of Oleuropein. This step mimicked the process occurring during olive drupes crushing in the first stage of oil production. The incubation of the enzymatic reaction mixture at a more acidic pH was subsequently performed, to simulate the conditions of olive paste malaxation during oil production. As a result, further isomeric forms were generated and the complex chromatographic profile typically observed for OA in olive oil extracts, including at least 13 different peaks/bands/groups of peaks, was carefully reproduced. Each of those chromatographic features could be subsequently assigned to specific types of OA-related isomers, belonging to one of four structurally different classes. Specifically, diastereoisomers/geometrical isomers corresponding to two different types of open-structure forms and to as many types of closed-structure, di-hydropyranic forms of OA, characterized by the presence of one or two carbonyl groups, according to the case, were evidenced. In addition, the presence of stable enolic/dienolic tautomers, providing an indirect structural confirmation for some OA isomers, was ascertained through RPLC-ESI-FTMS analyses performed under H/D exchange conditions, i.e. in the presence of deuterated water as one of the mobile phase solvents.


Assuntos
Acetatos/análise , Azeite de Oliva/análise , Piranos/análise , Acetatos/química , Acetatos/isolamento & purificação , Cromatografia de Fase Reversa/métodos , /isolamento & purificação , Deutério , Análise de Fourier , Hidrólise , Iridoides/química , Isomerismo , Extração Líquido-Líquido , Olea/química , Piranos/química , Piranos/isolamento & purificação , Espectrometria de Massas em Tandem/métodos , beta-Glucosidase/química
8.
Chem Biodivers ; 16(9): e1900266, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31298476

RESUMO

Two new spliceostatin analogs, designed as spliceostatins J and K (1 and 2), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 (3) and spliceostatin E (4). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS. Spliceostatin J (1) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4-b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA-MB-231 and A-549). Structure-activity-relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.


Assuntos
Antineoplásicos/farmacologia , Furanos/farmacologia , Lactonas/farmacologia , Pseudomonas/química , Pironas/farmacologia , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Furanos/isolamento & purificação , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Piranos/química , Piranos/isolamento & purificação , Piranos/farmacologia , Pironas/química , Pironas/isolamento & purificação , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade
10.
Carbohydr Res ; 482: 107728, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306897

RESUMO

The cell wall of Rathayibacter iranicus VKM Ac-1602T (family Microbacteriaceae, class Actinobacteria) is characterised by the absence of phosphate-containing and by the presence of two rhamnose-containing glycopolymers. The first is a branched rhamnomannan, in which 60% of mannose residues of the main chain are glycosylated by terminal mannose residues: →2)-α-D-Rhap-(1 → 3)-α-[α-D-Manp-(1 → 6)]-D-Manp-(1 → . The second is a branched teichuronic acid, in which all the rhamnose residues of the main chain are glycosylated by glucose residues:→3)-α-[α-D-Glcp-(1 → 2)]-L-Rhap-(1 → 4)-ß-D-GlcpA-(1 → 2)-α-D-Manp-(1 → 3)-α-D-Galp-(1 → 3)-ß-D-Glcp-(1 → . Both glycopolymers have the unique structures and described in the cell walls of Gram-positive bacteria for the first time. The obtained data allow for a more complete characterisation of the cell wall of the microorganism under investigation and can serve as a phenotypic characterisation of this bacterium. The glycopolymer structures were established using chemical and nuclear magnetic resonance (NMR) spectroscopy methods.


Assuntos
Actinobacteria/citologia , Parede Celular/química , Piranos/química , Ramnose/química , Sequência de Carboidratos , Glicosilação , Monossacarídeos/análise , Estereoisomerismo
11.
J Pharm Pharmacol ; 71(9): 1393-1399, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218683

RESUMO

OBJECTIVE: To evaluate the pharmacological characteristics of SU-011, a novel sodium-dependent glucose co-transporter 2 (SGLT2) inhibitor. METHODS: The in vitro activities of SU-011 were investigated in cell-based assays. The urinary glucose excretion, glucose tolerance and the risk of hypoglycaemia were evaluated in mice. Moreover, the dose-response relationship and chronic pharmacological studies of SU-011 were assessed in streptozotocin (STZ)-induced diabetic model, a STZ-treated model with impaired insulin secretion. KEY FINDINGS: SU-011 is a potential SGLT2 inhibitor with 5.6 nm inhibitory activity for SGLT2 and 1137-fold selectivity for SGLT1. In healthy mice, SU-011 improves the tolerance to a glucose load and promotes the urinary glucose excretion. Besides, SU-011 (10 mg/kg) still exhibited less risk of hypoglycaemia. During chronic treatment, SU-011 exhibited sustained glucose-lowering effect without the side effect of weight gain in STZ-induced diabetic mice. The levels of non-fasting and fasting plasma glucose, glycosylated haemoglobin, food and water intake were significantly decreased in SU-011-treated group. Moreover, SU-011 decreases the plasma levels of interleukin-1ß, tumour necrosis factor-α and C-reactive protein even better than that of dapagliflozin. CONCLUSIONS: All of these results indicated that SU-011 may be effective for the management of diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Piranos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Compostos Benzidrílicos/química , Compostos Benzidrílicos/farmacologia , Proteína C-Reativa , Diabetes Mellitus Experimental/sangue , Glucosídeos/química , Glucosídeos/farmacologia , Células HEK293 , Humanos , Interleucina-1beta/sangue , Masculino , Camundongos , Fragmentos de Peptídeos/sangue , Piranos/química , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Estreptozocina , Fator de Necrose Tumoral alfa/sangue
12.
Chem Biol Interact ; 309: 108718, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31211952

RESUMO

We have previously reported the isolation of four compounds, caffeoyloxy-5,6-dihydro-4-methyl-(2H)-pyran-2-one (CDMP), olinioside, caffeic acid and 3-hydroxylup-12-en-28-oic acid, from the leaves of Olinia usambarensis. Here, we evaluated the inhibitory effects of these compounds on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 macrophages, and found that CDMP is the most potent of these two pro-inflammatory mediators (IC50; 12.12 µM and 10.78 µM, respectively). Consistent with these results, CDMP also down-regulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6) at the protein and mRNA levels in LPS-treated RAW 264.7 macrophages. Furthermore, CDMP suppressed LPS-induced nuclear factor κB (NF-κB) activation by decreasing p65 nuclear translocation through the phosphorylation and degradation of the inhibitory κBα (IκBα). CDMP also attenuated LPS-induced transcriptional and DNA-binding activities of activator protein 1 (AP-1) by suppressing the phosphorylation and expression of c-Fos and c-Jun. Finally, CDMP considerably suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), but did not affect the phosphorylation of p38 or extracellular signal-regulated kinase (ERK). Taken together, our data suggest that CDMP down-regulates genes encoding pro-inflammatory mediators and cytokines, such as iNOS, COX-2, TNF-α, IL-1ß, and IL-6 via NF-κB and JNK/AP-1 inactivation in LPS-induced RAW 264.7 macrophages.


Assuntos
Mediadores da Inflamação/metabolismo , Myrtales/química , NF-kappa B/antagonistas & inibidores , Piranos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/antagonistas & inibidores , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Myrtales/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Piranos/química , Células RAW 264.7 , Fator de Transcrição AP-1/metabolismo
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 222: 117240, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31203053

RESUMO

Hypobromous acid (HOBr) is an important reactive oxygen species and has been recently found to be associated with a variety of diseases. However, owing to a lack of effective analytical tools, there is still limited understanding of its roles in living systems. Here, we present a new type of near-infrared fluorescent probe DCSN for HOBr detection. The designed probe exhibits high sensitivity with a low detection limit, excellent selectivity over other interfering species and low cytotoxicity. More interestingly, the fluorescence response behavior of the probe was different from the previous literatures due to the intramolecular charge transfer process. Moreover, we have successfully monitored HOBr in living cells by utilizing DCSN. This probe has potential to be used as a promising tool for better understanding the physiological functions of HOBr.


Assuntos
Benzopiranos/química , Bromatos/análise , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Limite de Detecção , Células MCF-7 , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Piranos/química , Espécies Reativas de Oxigênio/análise
14.
Food Chem Toxicol ; 130 Suppl 1: 110564, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199993

RESUMO

2-Isobutyl-4-methyltetrahydro-2H-pyran-4-ol) was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol is not genotoxic, does not have skin sensitization potential, and provided an MOE >100 for the repeated dose, developmental, and reproductive toxicity endpoints. The local respiratory toxicity endpoint was completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class III material (0.47 mg/day). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra and data on 2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol. The environmental endpoints were evaluated; 2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.


Assuntos
Perfumes/química , Perfumes/toxicidade , Piranos/química , Piranos/toxicidade , Animais , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Ratos , Medição de Risco , Pele/efeitos dos fármacos , Testes de Toxicidade
15.
Biomolecules ; 9(5)2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100934

RESUMO

4-oxo-4H-pyran-2.6-dicarboxylic acid (chelidonic acid, ChA) in the native state and in the complex with calcium [Ca(ChA)(H2O)3], named saucalchelin (CaChA), was isolated from the extract of Saussurea controversa leaves for the first time for the Asteraceae family. The structure of ChA was determined by NMR, MS and confirmed by X-ray analysis of its monomethyl ester, and CaChA was described by IR, ICP-MS, CHN analysis. The yield of ChA and CaChA was 45 mg/g and 70 mg/g of extract, respectively. The osteogenic activity of ChA, n-monobutyl ester of chelidonic acid, and CaChA has been studied in vitro in a 21-day culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in a standard nutrient medium without osteogenic supplements. CaChA significantly stimulated the growth of cell mass and differentiation of hAMMSCs into osteoblasts with subsequent mineralization of the culture and it may be a promising substance for accelerating bone tissue regeneration and engineering.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Piranos/farmacologia , Saussurea/química , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Extratos Vegetais/química , Piranos/química
16.
Eur J Med Chem ; 175: 187-200, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078866

RESUMO

The inability to discover novel class of antibacterial agents, especially against Gram-negative bacteria (GNB), compel us to consider a broader non-conventional approach to treat infections caused by multidrug-resistant (MDR) bacteria. One such approach is the use of adjuvants capable of revitalizing the activity of current existing antibiotics from resistant pathogens. Recently, our group reported a series of tobramycin (TOB)-based hybrid adjuvants that were able to potentiate multiple classes of legacy antibiotics against various MDR GNB. Herein, we report the modification of TOB-based hybrid adjuvants by replacing TOB domain by the pseudo-disaccharide nebramine (NEB) through selective cleavage of the α-d-glucopyranosyl linkage of TOB. Potent synergism was found for combinations of NEB-based hybrid adjuvants with multiple classes of legacy antibiotics including fluoroquinolones (moxifloxacin and ciprofloxacin), tetracyclines (minocycline), or rifamycin (rifampicin) against both wild-type and MDR P. aeruginosa clinical isolates. We also demonstrated that a combination of the optimized NEB-CIP hybrid 1b and rifampicin protects Galleria mellonella larvae from the lethal effects of extensively drug-resistant (XDR) P. aeruginosa. Mechanistic evaluation of NEB-based hybrid adjuvants revealed that the hybrids affect the outer- and inner membranes of wild-type P. aeruginosa PAO1. This study describes an approach to optimize aminoglycoside-based hybrids to yield lead adjuvant candidates that are able to resuscitate the activity of partner antibiotics against MDR GNB.


Assuntos
Antibacterianos/farmacologia , Dissacarídeos/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Piranos/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Sinergismo Farmacológico , Quimioterapia Combinada , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Larva/efeitos dos fármacos , Lepidópteros/crescimento & desenvolvimento , Lepidópteros/microbiologia , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Rifampina/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray , Suínos
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 220: 117108, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31146206

RESUMO

Near-Infrared "turn on" type fluorescent probes are attractive and promising in the fields of chemical sensing and bioimaging. Here, a new dicyanomethylene-4H-pyran derivative (DCM-Si) NIR fluorescent probe was designed and synthesized for specific lighting up F- in living cells and bodies. SiO bond was used as F- trigger, and the release of fluorophore (DCM-NH2) occurred after substituent reaction and subsequent 1,6-elimination. This NIR probe displayed high sensitivity and selectivity for the sensing of F-, and the detection limit was calculated to be as low as 157 nM. Moreover, the "off-on" fluorescent signal changes can be realized by adding F- in living cells and zebrafish embryos.


Assuntos
Corantes Fluorescentes/química , Fluoretos/análise , Imagem Molecular/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Embrião não Mamífero , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Fluoretos/química , Células HeLa , Humanos , Limite de Detecção , Piranos/química , Sensibilidade e Especificidade , Dióxido de Silício/química , Espectrofotometria Ultravioleta , Peixe-Zebra/embriologia
18.
Chemistry ; 25(39): 9272-9279, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31099933

RESUMO

There is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C-terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C-6. Our strategy uses levoglucosan as inexpensive starting material and facilitates an approach to complex carbohydrate analogues with multiple C-F bonds. The challenge of our synthetic route centered around an efficient preparation of crucial 1,6-anhydro-2,4-dideoxy-difluoroglucopyranose and focused on achieving a difficult glycosylation of the trifluoroallopyranose donor. The results clearly highlight challenges related to the preparation of polyhalogenated complex organic molecules and pave the way to access novel medically relevant tools.


Assuntos
Carboidratos/química , Glucose/química , Dissacarídeos/química , Fluoretação , Glucose/análogos & derivados , Glicoconjugados/química , Piranos/química , Estereoisomerismo
19.
Phytochemistry ; 163: 187-194, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31014820

RESUMO

Smoke derived karrikinolide and trimethylbutenolide exerted neuroprotective effects against monoamine oxidase and acetylcholinesterase. Synthesis of potent analogs was achieved. Sulphur substitution in the bicyclic ring structure of KAR1 displayed the most encouraging activity returning IC50 values of 13.75 ±â€¯0.001 µM and 0.03 ±â€¯0.02 µM for monoamine oxidase A and B and 0.08 ±â€¯0.006 µM for acetylcholinesterase. Neuroprotective butenolides may be particularly useful in the treatment of depressive disorders, Alzheimer's and Parkinson's diseases.


Assuntos
4-Butirolactona/análogos & derivados , Transtorno Depressivo/tratamento farmacológico , Furanos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Piranos/farmacologia , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Acetilcolinesterase/metabolismo , Relação Dose-Resposta a Droga , Furanos/síntese química , Furanos/química , Humanos , Estrutura Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Piranos/síntese química , Piranos/química , Relação Estrutura-Atividade
20.
Molecules ; 24(7)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30934989

RESUMO

An ultra-high-performance liquid chromatographic (UHPLC) separation was developed for six kava pyrones (methysticin, dihydromethysticin (DHM), kavain, dihydrokavain (DHK), desmethoxyyangonin (DMY), and yangonin), two unidentified components, and three Flavokavains (Flavokavain A, B, and C) in Piper methysticum (kava). The six major kavalactones and three flavokavains are completely separated (Rs > 1.5) within 15 min using a HSS T3 column and a mobile phase at 60 °C. All the peaks in the LC chromatogram of kava extract or standard solutions were structurally confirmed by LC-UV-MS/MS. The degradations of yangonin and flavokavains were observed among the method development. The degradation products were identified as cis-isomerization by MS/MS spectra. The isomerization was prevented or limited by sample preparation in a non-alcoholic solvent or with no water. The method uses the six kava pyrones and three flavokavains as external standards. The quantitative calibration curves are linear, covering a range of 0.5⁻75 µg/mL for the six kava pyrones and 0.05⁻7.5 µg/mL for the three flavokavains. The quantitation limits for methysticin, DHM, kavain, DHK, DMY, and yangonin are approximately 0.454, 0.480, 0.277, 0.686, 0.189, and 0.422 µg/mL. The limit of quantification (LOQs) of the three flavokavains are about 0.270, 0.062, and 0.303 µg/mL for flavokavain C (FKC), flavokavain A (FKA), and flavokavain B (FKB). The average recoveries at three different levels are 99.0⁻102.3% for kavalactones (KLs) and 98.1⁻102.9% for flavokavains (FKs). This study demonstrates that the method of analysis offers convenience and adequate sensitivity for determining methysticin, DHM, kavain, DHK, yangonin, DMY, FKA, FKB, and FKC in kava raw materials (root and CO2 extract) and finished products (dry-filled capsule and tablet).


Assuntos
Flavonoides/química , Kava/química , Lactonas/química , Extratos Vegetais/química , Dióxido de Carbono/química , Cromatografia Líquida de Alta Pressão/métodos , Isomerismo , Limite de Detecção , Estrutura Molecular , Raízes de Plantas/química , Piranos/química , Pironas/química , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem/métodos
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