Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.160
Filtrar
1.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500647

RESUMO

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 µM, and with IC50 values of 12.6 ± 0.2 µM-27.6 ± 1.1 µM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 µM), with a potency (IC50 = 12.6 ± 0.2 µM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 µM). The study of the structure-activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.


Assuntos
Fármacos Antiobesidade/farmacologia , Diabetes Mellitus/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Isoxazóis/farmacologia , alfa-Amilases/antagonistas & inibidores , Fármacos Antiobesidade/química , Diabetes Mellitus/metabolismo , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/química , Isoxazóis/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
2.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443347

RESUMO

α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a-m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a-m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 µM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 µM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.


Assuntos
Amidas/química , Benzimidazóis/química , Benzimidazóis/farmacologia , Desenho de Fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Sais/química , Benzimidazóis/metabolismo , Domínio Catalítico , Inibidores de Glicosídeo Hidrolases/metabolismo , Cinética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
3.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361791

RESUMO

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.


Assuntos
Benzaldeídos/farmacologia , Benzofuranos/farmacologia , Glicemia/análise , Catecóis/farmacologia , Depsídeos/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores de Glicosídeo Hidrolases/farmacologia , Monitorização Ambulatorial/métodos , alfa-Glucosidases/sangue , Acarbose/química , Acarbose/farmacologia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Sítios de Ligação , Técnicas Biossensoriais/instrumentação , Catecóis/química , Catecóis/isolamento & purificação , Depsídeos/química , Depsídeos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrólise , Cinética , Maltose/metabolismo , Simulação de Acoplamento Molecular , Monitorização Ambulatorial/instrumentação , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica , Dispositivos Eletrônicos Vestíveis , alfa-Glucosidases/química
4.
Molecules ; 26(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34299396

RESUMO

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-ß-d-glucopyranosyl-(1→2)-ß-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C13-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6'-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC50 3.4 ± 0.2 µM) compared to the reference standard acarbose (IC50 5.9 ± 0.1 µM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 µM, compared to acarbose (IC50 665 ± 42 µM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC50 of 94.7 ± 1.3 and 85.3 ± 2.4 µM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC50 > 100 µM).


Assuntos
Abietanos/química , Antineoplásicos/farmacologia , Inibidores da Colinesterase/farmacologia , Clerodendrum/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Folhas de Planta/química , Humanos , Neoplasias/tratamento farmacológico , Células Tumorais Cultivadas , alfa-Amilases/antagonistas & inibidores
5.
Molecules ; 26(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299476

RESUMO

In this study, the health-promoting benefits of different fruits grown in Madeira Island, namely lemon (Citrus limon var. eureka), tangerine (Citrus reticulata var. setubalense), pitanga (Eugenia uniflora var. red), tomato (Solanum lycopersicum var. gordal) and uva-da-serra, an endemic blueberry (Vaccinium padifolium Sm.), were investigated. The phenolic composition (total phenolics and total flavonoids content) and antioxidant capacity (assessed through ABTS and DPPH assays) were measured revealing a high phenolic potential for all fruits, except tomato, while uva-da-serra is particularly rich in flavonoids. In relation to the antioxidant capacity, the highest values were obtained for pitanga and uva-da-serra extracts. The bioactive potential was also assessed through the ability of the extracts to inhibit digestive enzymes linked to diabetes (α-amylase, α- and ß-glucosidases) and hypertension (angiotensin-converting enzyme, ACE). The results obtained point to a very high bioactive potential with the selected samples exhibiting very important ACE anti-enzymatic capacities. A statistical analysis of the obtained data reveals a very strong correlation between ABTS and TPC, and a strong contribution of the fruit polyphenols for enzyme inhibition, and thus, presenting high antihypertensive and antidiabetic capacities. Overall, the results obtained clearly show a high bioactive potential of the selected fruits that should be further studied, in terms of specific phenolic composition. Moreover, these results strongly support the valorisation of pitanga seeds usually discarded as a waste, and uva-da-serra, an endemic and wild bush, as potential bioresources of bioactive compounds with impact in human diet.


Assuntos
Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Flavonoides/farmacologia , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , alfa-Amilases/antagonistas & inibidores , Humanos
6.
Molecules ; 26(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299456

RESUMO

The inhibition of certain digestive enzymes by target food matrices represents a new approach in the treatment of socially significant diseases. Proving the ability of fruits to inhibit such enzymes can support the inclusion of specific varieties in the daily diets of patients with diabetes, obesity, Alzheimer's disease, etc., providing them with much more than just valuable micro- and macromolecules. The current study aimed atidentifying and comparing the GC-MS metabolic profiles of eight peach varieties ("Filina", "Ufo 4, "Gergana", "Laskava", "July Lady", "Flat Queen", "Evmolpiya", and "Morsiani 90") grown in Bulgaria (local and introduced) and to evaluate the inhibitory potential of their extracts towards α-glucosidase, α-amylase, lipase, and acetylcholinesterase. In order to confirm samples' differences or similarities, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also applied to the identified metabolites. The results provide important insights into the metabolomic profiles of the eight peach varieties and represent a first attempt to characterize the peels of the peach varieties with respect to α-glucosidase-, α-amylase-, lipase-, and acetylcholinesterase-inhibitory activities. All of the studied peach extracts displayed inhibitory activity towards α-glucosidase (IC50: 125-757 mg/mL) and acetylcholinesterase (IC50: 60-739 mg/mL), but none of them affected α-amylase activity. Five of the eight varieties showed inhibitory activity towards porcine pancreatic lipase (IC50: 24-167 mg/mL). The obtained results validate the usefulness of peaches and nectarines as valuable sources of natural agents beneficial for human health, although further detailed investigation should be performed in order to thoroughly identify the enzyme inhibitors responsible for each activity.


Assuntos
Extratos Vegetais/farmacologia , Prunus persica/metabolismo , Acetilcolinesterase/metabolismo , Amilases/metabolismo , Antioxidantes/farmacologia , Bulgária , Inibidores da Colinesterase/farmacologia , Inibidores Enzimáticos/farmacologia , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Inibidores de Glicosídeo Hidrolases/farmacologia , Lipase/antagonistas & inibidores , Lipase/metabolismo , Metaboloma , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prunus persica/química , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
7.
J Asian Nat Prod Res ; 23(8): 724-730, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34253100

RESUMO

Three new flavonoid glycosides, embeliaflavosides A-C (1-3), together with eight known flavonoid glycosides (4-11), were isolated from the fruits of Embelia ribes. Their structures were established based on the analyses of spectroscopic data. Compounds 1-11 were evaluated for antioxidant and α-glucosidase inhibitory activities. The results revealed that compounds 1-11 owned significant ABTS radical scavenging activity with IC50 values of 2.52-9.78 µM, and DPPH scavenging activity with IC50 values of 7.56-26.47 µM, respectively. However, α-glucosidase inhibition assay indicated that all the isolates were inactive.[Formula: see text].


Assuntos
Embelia , Ribes , Antioxidantes/farmacologia , Embelia/metabolismo , Flavonoides/farmacologia , Frutas , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Estrutura Molecular , Extratos Vegetais , Ribes/metabolismo , alfa-Glucosidases/metabolismo
8.
Food Chem ; 361: 130144, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082387

RESUMO

Effect of high-intensity ultrasound (HIU) compared with thermal treatments on baobab fruit pulp (BFP) quality and bioactive properties were investigated. HIU treatments, particularly at intensities of 687.5 W/cm2 for 5 min, and 344 W/cm2 for 15 min significantly (p < 0.05) increased the cloudiness index, ascorbic acid (AA) retention, total phenolic and flavonoid contents, and antioxidant capacity besides a more potent α-amylase and α-glucosidase inhibition relative to thermally treated samples. Moreover, the physicochemical parameters, colour index, and browning index were maintained with HIU besides lower 5-hydroxymethylfurfural values than thermal processing. HPLC analysis revealed that the content of most phenolic compounds was the highest in HIU treatments besides a 235-256% increase in procyanidin C1 compared with control samples. The AA retention following HIU treatments was 87.62-102.86% compared to 30.47-61.90% in thermally treated samples. Our analyses portrayed ultrasound as a feasible alternative to conventional thermal processing of BFP.


Assuntos
Adansonia/química , Inibidores Enzimáticos/farmacologia , Frutas/química , Ultrassom/métodos , alfa-Amilases/antagonistas & inibidores , Antioxidantes/análise , Antioxidantes/química , Ácido Ascórbico/análise , Biflavonoides/análise , Catequina/análise , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Flavonoides/análise , Inibidores de Glicosídeo Hidrolases/análise , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Fenóis/análise , Proantocianidinas/análise , alfa-Glucosidases/metabolismo
9.
Molecules ; 26(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065194

RESUMO

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 µM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 µM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.


Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , Tiazinas/química , Tiazinas/farmacologia , Acetamidas/química , Acetamidas/uso terapêutico , Simulação por Computador , Diabetes Mellitus/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tiazinas/síntese química
10.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064448

RESUMO

The 2-amino-5-(3/4-fluorostyryl)acetophenones were prepared and reacted with benzaldehyde derivatives to afford the corresponding 5-styryl-2-aminochalcone hybrids. The trans geometry of the styryl and α,ß-unsaturated carbonyl arms, and the presence of NH…O intramolecular hydrogen bond were validated using 1H-NMR and X-ray data. The 2-amino-5-styrylacetophenones and their 5-styryl-2-aminochalcone derivatives were screened in vitro for their capability to inhibit α-glucosidase and/or α-amylase activities. Their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. Kinetic studies of the most active derivatives from each series against α-glucosidase and/or α-amylase activities have been performed supported by molecular docking studies to determine plausible protein-ligand interactions on a molecular level. The key aspects of the pharmacokinetics of these compounds, i.e., absorption, distribution, metabolism, and excretion have also been simulated at theoretical level. The most active compounds from each series, namely, 2a and 3e, were evaluated for cytotoxicity against the normal monkey kidney cells (Vero cells) and the adenocarcinomic human epithelial (A549) cell line to establish their safety profile at least in vitro.


Assuntos
Antioxidantes/farmacologia , Carboidratos/química , Chalconas/síntese química , Chalconas/farmacologia , Simulação por Computador , Inibidores Enzimáticos/farmacologia , Receptores de Droga/química , Células A549 , Animais , Morte Celular/efeitos dos fármacos , Chalconas/química , Chalconas/farmacocinética , Chlorocebus aethiops , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Termodinâmica , Células Vero , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo
11.
Fitoterapia ; 153: 104963, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34129922

RESUMO

Six undescribed low-polarity compounds including three rare 14-methylergostane steroids (1-3), one euphane triterpenoid (4) and two octadecanoic acid ethyl esters (5 and 6), along with ten previously reported terpenyl cometabolites (7-16), were isolated from the stems of Tinospora sagittata. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known compounds, and all of them have been reported from T. sagittata for the first time. Compounds 4-6 and 16 showed potent in vitro inhibitory activity against the diabetes target α-glucosidase, while compounds 10 and 14 displayed promising antibacterial effect toward Staphylococcus aureus ATCC 25923.


Assuntos
Antibacterianos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Tinospora/química , Antibacterianos/isolamento & purificação , China , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Staphylococcus aureus/efeitos dos fármacos
12.
Int J Biol Macromol ; 185: 194-205, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34166690

RESUMO

Steam explosion (SE) was a friendly environmentally pretreatment method. In this study, the effect of steam explosion (SE) pretreatment on structure and α-glucosidase inhibitory activity of Ampelopsis grossedentata polysaccharides was evaluated. Two novel polysaccharides (AGP and AGP-SE) were extracted, isolated, purified and analyzed by NMR, FT-IR and methylation. The results indicated that AGP mainly consisted of Rha, Xyl, Glc, and Ara with a molecular weight of 2.74 × 103 kDa and AGP-SE mainly consisted of Man, Ara, and Gal with a molecular weight of 2.14 × 103 kDa. Furthermore, the backbone of AGP and AGP-SE were mainly composed of 5)-Araf-(1→, -Glcp-(1→, 6)-Glcp-(1→, 6)-Galp-(1→, 3,6)-Manp-(1→, and 2,3,6)-Glcp-(1→. Finally, we demonstrated that all polysaccharides exhibited obviously α-glucosidase inhibition activity and mixed type inhibition. AGP-SE had better α-glucosidase inhibition activity and the binding affinity KD on α-glucosidase by using Surface Plasmon Resonance (SPR) than AGP. Overall, SE pretreatment is an effective method for extracting polysaccharide and provides a new idea into the improvement of biological activity.


Assuntos
Ampelopsis/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Polissacarídeos/farmacologia , alfa-Glucosidases/metabolismo , Sequência de Carboidratos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Metilação , Peso Molecular , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Vapor , Ressonância de Plasmônio de Superfície
13.
Int J Biol Macromol ; 184: 380-392, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34126149

RESUMO

Russula virescens is an edible wild mushroom that is widely distributed in south of China. This research aimed to analyze the structure characterization and evaluate the hypoglycemic, anticancer and immunological activities of two water soluble polysaccharides RVP-1 and RVP-2 from R. virescens. The results showed RVP-1 and RVP-2 were non-triple helix structured hetero-polysaccharides with different weight-average molecular weight 14,883 and 13,301 Da, respectively. Both RVP-1 and RVP-2 were composed of galactose, glucose, mannose and fructose, and the sugar residues were mainly linked by 1,6→, 1,2→, 1→ and 1,3,6→ glycosidic bonds. Moreover, the antidiabetic, anticancer and immune activities of RVP-1 and RVP-2 were explored in vitro methods. The two polysaccharides have potential for inhibiting α-glucosidase and α-amylase activities, suppressing HepG-2, A549 and MCF-7 cancer cells proliferation, and activating macrophage RAW 264.7 cells to secret immune cytokines for mediating cellular immune response. These findings provided a scientific basis for further utilization of polysaccharide from R. virescens.


Assuntos
Antineoplásicos/química , Antioxidantes/química , Basidiomycota/química , Citocinas/metabolismo , Polissacarídeos Fúngicos/química , Hipoglicemiantes/química , Células A549 , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Sequência de Carboidratos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Polissacarídeos Fúngicos/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Células MCF-7 , Camundongos , Peso Molecular , Células RAW 264.7 , alfa-Amilases/antagonistas & inibidores
14.
Chem Biodivers ; 18(6): e2100252, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33988294

RESUMO

Leptosparones A-F (1-6), six new dimeric acylphloroglucinol derivatives with unprecedented skeletons, were isolated from Leptospermum scoparium. Compounds 1-3 and 5-6 are phenylpropanoyl-phloroglucinol dimers, while 4 is a phenylpropanoylphloroglucinol-isovalerylphloroglucinol hybrid. Structurally, these compounds represent the first examples of dimeric phloroglucinols with unprecedented C(7')-C(8) linkage between the phloroglucinol core and the acyl side chain. Their structures were elucidated by comprehensive analyses of spectroscopic data, single crystal X-ray diffraction and chemical calculations. In addition, all compounds showed inhibitory effects against α-glucosidase with IC50 values ranging from 39.5 to 186.8 µM.


Assuntos
Inibidores de Glicosídeo Hidrolases/farmacologia , Leptospermum/química , Floroglucinol/farmacologia , alfa-Glucosidases/metabolismo , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Modelos Moleculares , Estrutura Molecular , Floroglucinol/síntese química , Floroglucinol/química
15.
Fitoterapia ; 152: 104912, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33933538

RESUMO

The first phytochemical investigation from the stems of Croton krabas resulted in the isolation of three new ent-clerodane diterpenoids, crotonkrabases A-C (1-3), along with two known compounds, 12-oxohardwickiic acid (4) and crotonpyrone B (5). Their structures were elucidated using extensive spectroscopic methods. The structure of 3 was unambiguously proven by X-ray crystallography. Furthermore, the absolute configurations of compounds 1-3 were identified by NOESY and the comparison of their experimental ECD spectra with those of calculated ECD spectra reported in the literature. Compounds 1, 2, and 5 showed antibacterial activities against two Gram-positive bacteria (Bacillus cereus and Bacillus subtilis); whereas compound 4 exhibited weak antibacterial against B. cereus. In addition, compound 4 showed potent α-glucosidase inhibitory activity, which was lower than the reference standard acarbose.


Assuntos
Antibacterianos/farmacologia , Croton/química , Diterpenos Clerodânicos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Antibacterianos/isolamento & purificação , Bacillus/efeitos dos fármacos , Diterpenos Clerodânicos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Tailândia
16.
Fitoterapia ; 153: 104946, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34048830

RESUMO

Four new alkaloids, nonialkaloids A-D (1-4) and six known analogues (5-10) were isolated from the noni juice. Among the new compounds, 1 and 2 are indole alkaloids with a seven-membered fused N-heterocyclic ring, 3 and 4 are quaternary ammonium derivatives. The structures were elucidated by extensive NMR and MS analysis, while the absolute configurations of the stereogenic carbons were established based on quantum-chemical electronic circular dichroism calculations or the modified Mosher's method. All the isolates were tested for α-glucosidase inhibitory activities. Compounds 1 and 3 displayed potent inhibitory activity against α-glucosidase with the IC50 values of 413.7 and 364.4 µM, respectively.


Assuntos
Inibidores de Glicosídeo Hidrolases/farmacologia , Alcaloides Indólicos/farmacologia , Morinda/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
17.
ACS Appl Mater Interfaces ; 13(22): 25624-25634, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34043318

RESUMO

A highly stable and reusable fluorescent multisample nanobiosensor for the detection of α-glucosidase inhibitors has been developed by coupling fluorescent liposomal nanoparticles based on conjugated polymers (L-CPNs) to the enzyme α-glucosidase, one of the main target enzymes in the treatment of type 2 diabetes. The mechanism of sensing is based on the fluorescence "turn-on" of L-CPNs by p-nitrophenol (PNP), the end product of the enzymatic hydrolysis of p-nitrophenyl-α-d-glucopyranoside. L-CPNs, composed of lipid vesicles coated with a blue-emitting cationic polyfluorene, were designed and characterized to obtain a good response to PNP. Two nanobiosensor configurations were developed in this study. In the first step, a single-sample nanobiosensor composed of L-CPNs and α-glucosidase entrapped in a sol-gel glass was developed in order to characterize and optimize the device. In the second part, the nanobiosensor was integrated and adapted to a multiwell microplate and the possibility of reusing it and performing multiple measurements simultaneously with samples containing different α-glucosidase inhibitors was investigated. Using super-resolution confocal microscopy, L-CPNs could be visualized within the sol-gel matrix, and the quenching of their fluorescence, induced by the substrate, was directly observed in situ. The device was also shown to be useful not only as a platform for screening of antidiabetic drugs but also for quantifying their presence. The latter application was successfully tested with the currently available drug, acarbose.


Assuntos
Técnicas Biossensoriais/métodos , Fluorescência , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Nanopartículas/administração & dosagem , Polímeros/química , alfa-Glucosidases/química , Acarbose/farmacologia , Fluorenos/química , Corantes Fluorescentes , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/isolamento & purificação , Lipossomos/química , Nanopartículas/química , alfa-Glucosidases/análise
18.
Food Chem ; 361: 130047, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029903

RESUMO

Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from white, green, oolong, black tea, were investigated by using rat intestinal enzymes and human Caco-2 cells. Regarding rat intestinal enzyme mixture, all four tea extracts were very effective in inhibiting maltase and glucoamylase activity, but only white tea extract inhibited sucrase and isomaltase activity and the inhibition was limited. Mixed-type inhibition on rat maltase activity was observed. Tea extracts in combination with acarbose, produced a synergistic inhibitory effect on rat maltase activity. Caco-2 cells experiments were conducted in Transwells. Green tea extract and epigallocatechin gallate show dose-dependent inhibition on human sucrase activity, but no inhibition on rat sucrase activity. The opposite was observed on maltase activity. The results highlighted the different response in the two investigated model systems and show that tea polyphenols are good inhibitors for α-glucosidase activity.


Assuntos
Glicosídeo Hidrolases/antagonistas & inibidores , Intestinos/enzimologia , Extratos Vegetais/química , Polifenóis/farmacologia , Chá/química , Acarbose/farmacologia , Animais , Células CACO-2 , Catequina/análogos & derivados , Catequina/farmacologia , Glucana 1,4-alfa-Glucosidase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Cinética , Oligo-1,6-Glucosidase/antagonistas & inibidores , Ratos , Sacarase/antagonistas & inibidores , alfa-Glucosidases/efeitos dos fármacos
19.
Int J Biol Macromol ; 183: 1548-1559, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34029582

RESUMO

In this study, hot water, 0.1 M HCl and 0.1 M NaOH and 0.1 M NaCl solution were separately used for extraction of blackberry polysaccharides (BPs: Hw, Ac, Al and Na). The physicochemical properties and biological activities were then investigated and compared. Results showed that the extraction yield, molecular weight, monosaccharide composition, particle size, triple-helical structure, surface morphology and rheological properties of BPs were greatly affected by extraction solvents. Bioactivity assays implied that the four BPs showed that the polysaccharides (Hw and Na) with higher molecular weight had stronger antioxidant and α-glucosidase inhibitory activity. Moreover, anti-glycated assay indicated that BPs with higher molecular weight and higher content of galacturonic acid possessed better inhibition of AGEs formation. These results suggested that the higher molecular weight of blackberry polysaccharide could be developed as a beneficial bioactive ingredient for diabetes mellitus and complications.


Assuntos
Antioxidantes/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Polissacarídeos/farmacologia , Rubus/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Configuração de Carboidratos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Tamanho da Partícula , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Água/química , alfa-Glucosidases/metabolismo
20.
Colloids Surf B Biointerfaces ; 205: 111847, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34022705

RESUMO

In this work, a simple and rapid screening strategy was developed combining capillary electrophoresis analysis with enzymatic assay based on immobilized α-glucosidase. For α-glucosidase immobilization, magnetic core-shell metal-organic frameworks composite (Fe3O4@CS@ZIF-8) was fabricated by a step-by-step assembly method, and α-glucosidase was in situ encapsulated in crystal lattice of ZIF-8. The composite was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and vibrating sample magnetometer. After immobilization, α-glucosidase exhibited enhanced tolerance to temperature and pH, and its reusability was greatly improved with 74 % of initial enzyme activity after being recycled 10 times. The Michaelis-Menten constant of immobilized enzyme was calculated to be 0.47 mM and its inhibition constant and IC50 for acarbose were 0.57 µM and 0.18 µM, respectively. The immobilized enzyme was subsequently applied to inhibitor screening from 14 TCMs, and Rhei Radix et Rhizoma was screened out. Among the commercially available 10 components presented in Rhei Radix et Rhizoma, gallic acid, (+)-catechin and epicatechin exhibited the strongest inhibitory effect on α-glucosidase. Their binding sites and modes with α-glucosidase were simulated via molecular docking to further verify the inhibition screening assay results. The positive results indicated that the Fe3O4@CS@ZIF-8-based screening strategy may provide a new avenue for discovering enzyme inhibitors from TCMs.


Assuntos
Estruturas Metalorgânicas , alfa-Glucosidases , China , Enzimas Imobilizadas , Inibidores de Glicosídeo Hidrolases/farmacologia , Fenômenos Magnéticos , Simulação de Acoplamento Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...