Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.194
Filtrar
1.
Food Chem ; 370: 130981, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34500290

RESUMO

In the present study, 14 structurally unique flavonoids were screened to systematically investigate structural requirements for selectively inhibiting human α-amylase versus α-glucosidase to obtain a slow but complete starch digestion for health benefit. The selective inhibition property of three flavonoids chosen against the two classes of starch digestive enzymes was confirmed through various analytical techniques - in vitro inhibition assay, fluorescence quenching, kinetic study, and molecular modeling. Considering the chemical structure of flavonoids, the double bond between C2 and C3 and OH groups at A5 and B3 are critical for the inhibition of α-amylase allowing flavonoids to lie parallel on the α-amylase catalytic active site, whereas the OH groups at B3 and C3 are important for α-glucosidase inhibition causing B-ring specific entry into the catalytic active site of α-glucosidase. Our findings provide insights into how to apply flavonoids to effectively control digestion rate for improving physiological responses.


Assuntos
alfa-Amilases , alfa-Glucosidases , Flavonoides , Humanos , Amido
2.
Food Chem ; 370: 130979, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543921

RESUMO

Hops are abundant in natural bioactive compounds. In this work, nine prenylated bitter compounds from hop were evaluated for their inhibitory activity against α-glucosidase. As a result, four flavonoids and one phloroglucinol (lupulone, LP) outperformed acarbose in inhibiting α-glucosidase. Isoxanthohumol (IX) and LP with two types of structures were selected for inhibition mechanism studies by spectroscopic methods and molecular dynamics simulation (MD). Results showed that IX acted as noncompetitive inhibitor and bound to α-glucosidase in allosteric sites via hydrogen bonds, hydrophobic, van der Waals (vdW), and electrostatic force, whereas LP was uncompetitive inhibitor and bound to catalytic sites via hydrophobic and vdW interactions. Notably, the conformation around binding site of α-glucosidase formed stable α-helix and tightened after binding IX and LP, respectively, which helped to elucidate noncompetitive and uncompetitive inhibitory mechanisms. This work demonstrated that two types of prenylated bitter compounds are discrepant in their mechanisms of interaction with α-glucosidase.


Assuntos
Humulus , Simulação por Computador , Flavonoides , Paladar , alfa-Glucosidases
3.
Food Chem ; 372: 131231, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624776

RESUMO

Phenolic acids are involved in modulating the activity of starch digestive enzymes but remains unclear if their interaction with enzymes or starch is governing the inhibition. The potential inhibition of nine phenolic acids against α-amylase and α-glucosidase was studied applying different methodologies to understand interactions between phenolic acids and either enzymes or substrates. Vanillic and syringic acids were prone to interact with α-amylase requiring low half-maximum inhibitory concentration (IC50) to inhibit starch hydrolysis. Nevertheless, the initial interaction of phenolic acids with starch somewhat obstructed their interaction with starch, requiring 10 times higher IC50, with the exception of chlorogenic and gallic acid. The study demonstrates that 10% of the phenolic acids were retained during starch gelatinization. Those effects were not really evident with α-glucosidase, likely due to the small molecular size of maltose substrate. Phenolic acids with > 1 hydroxyl group like caffeic and protocatechuic acids showed the lowest IC50 against α-glucosidase.


Assuntos
alfa-Amilases , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases , Hidrólise , Maltose , Amido
4.
Food Chem ; 372: 131334, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638063

RESUMO

Due to the poor lipophilicity of chlorogenic acid (CA), five CA derivatives (C2-CA, C4-CA, C6-CA, C8-CA, and C12-CA) with different lipophilicities were synthesized using acylation catalyzed by lipase in present study. The inhibitory activities and mechanisms of CA and its derivatives on α-amylase and α-glucosidase were then determined. Results showed that the inhibitory activities of CA derivatives on α-amylase and α-glucosidase were enhanced as lipophilicity increased, and the inhibitory activities of C12-CA were stronger than those of CA. IC50 values of C12-CA were 13.30 ± 0.26 µmol/mL for α-amylase and 3.42 ± 0.10 µmol/mL for α-glucosidase. C12-CA possessed the smallest Kic and Kiu values, and its inhibitory actions on α-amylase and α-glucosidase were stronger than those of CA and the other derivatives. Effects of C12-CA on microenvironments of amino acid residues and secondary structures of α-amylase and α-glucosidase were greater than those of CA and the other derivatives.


Assuntos
alfa-Amilases , alfa-Glucosidases , Ácido Clorogênico , Inibidores de Glicosídeo Hidrolases , Lipase
5.
Food Chem ; 372: 131294, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638068

RESUMO

This study renewed focus on Allmania nodiflora, a green leafy vegetable with diverse nutritional and medicinal properties. The bioaccessibility and the impact of in vitro simulated digestion on polyphenolics were investigated and identified using LC-MS. Although in vitro digestion reduced polyphenolics, the pancreatic digested sample showed a significant bioaccessibility of 97% with better metal ion binding activity (99%). Increased α-amylase and α-glucosidase inhibition (>45%) potentials were also observed in the digested samples. The presence of compounds such as rutin, caffeic acid, catechin, saikosaponin was also identified to be responsible for the enzyme inhibition against postprandial hyperglycemia. These results indicated that the pH of the digestive buffers is responsible for the structural changes in polyphenols for assimilation in the intestine. Hence, A. nodiflora leaf could serve as a functional food having higher assimilated polyphenolics with abundant therapeutic potential, which would be indispensible for future nutraceutical product development from green leafy vegetables.


Assuntos
Polifenóis , alfa-Glucosidases , Digestão , Cinética , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
6.
Food Chem ; 372: 131316, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653778

RESUMO

A more accurate HPLC-MS screening method combining functional enzyme assay and affinity ultrafiltration screening assay was developed and applied for the screening of natural product inhibitors of α-glucosidase from Cercis chinensis Bunge fruits. The enzyme assay was conducted to prescreen botanical extracts, in which maltose was used as the substrate and detection object. That showed the Cercis chinensis Bunge fruits demonstrated higher α-glucosidase inhibitory activity (IC50 = 11.94 ± 1.23 µg/mL) than acarbose (IC50 = 44.03 ± 4.37 µg/mL) (n = 3, p < 0.05). Subsequently, twelve bioactive components targeting α-glucosidase were screened out and identified using affinity ultrafiltration coupled to liquid chromatography-mass spectrometry. The known inhibitor, acarbose, was used as a positive control and competitive ligand to eliminate false positives. Moreover, bindings of the twelve components to the active site of α-glucosidase were investigated via molecular docking, which further confirmed the results of the screening assay.


Assuntos
Inibidores de Glicosídeo Hidrolases , Ultrafiltração , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos , Frutas , Simulação de Acoplamento Molecular , Extratos Vegetais , Espectrometria de Massas em Tandem , alfa-Glucosidases
7.
Food Chem ; 371: 131128, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563970

RESUMO

Lithocarpus polystachyus Rehd. known as Sweet Tea in China has attracted lots of interest for its good hypoglycemic effect and the potential as a hypoglycemic agent. Based on affinity separation-UPLC-Q-TOF-MS/MS, 54 potential α-glucosidase inhibitiors were identified and 44 were structurally determined. Out of them, 41 were identified for the first time from this plant including flavonoids, fatty acids, triterpenes, alkaloids, and coumarins. Enzyme assays revealed that flavonoids exhibited higher inhibitory activity against α-glucosidase than others with astilbin (IC50 = 6.14 µg·mL-1), morin (IC50 = 8.46 µg·mL-1), and naringenin (IC50 = 10.03 µg·mL-1) showing 2- to 4-fold higher potency than the positive control acarbose. They were proved as reversible inhibitors with mixed inhibition mechanism. Ki (Ki') values and molecular dockings strongly supported the potency order of astilbin, morin and naringenin that showed in the enzyme assays.


Assuntos
Fagaceae , Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Extratos Vegetais , Folhas de Planta , Espectrometria de Massas em Tandem , alfa-Glucosidases
8.
J Sci Food Agric ; 102(1): 53-61, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34031881

RESUMO

BACKGROUND: Corn silk is a very important by-product of corn production with medicinal value. Corn silk polysaccharide (CSP) is the main active ingredient. In the present study, ultrasound and spheroidization by anti-solvent were applied to improve the biological activity of CSP. RESULTS: The results showed that ultrasonic degradation improved the α-glucosidase inhibitory activity of CSP by changing its physicochemical characteristics. As the anti-solvent ratio increased, the particle size of the nanoparticles (NPs) from the spheroidization of ultrasonic-degraded corn silk polysaccharide (UCSP) gradually increased, and NP-1 exhibited the highest inhibitory effect of α-glucosidase. Isothermal titration calorimetry (ITC) results indicated that the enhanced activity might be due to more α-glucosidase binding sites with NP-1 compared with no spheroidization. Western blotting results showed that NP-1 could improve the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) uptake in the L6 cells by regulating the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and the translocation of glucose transporter 4 (GLUT4). NP-1 also exhibited excellent stability in different environments. CONCLUSION: The study revealed that ultrasonic treatment and spheroidization processing showed potential applications for improving the biological activity of polysaccharides. © 2021 Society of Chemical Industry.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Zea mays/química , Animais , Transporte Biológico/efeitos dos fármacos , Linhagem Celular , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Ultrassom , alfa-Glucosidases/química
9.
Food Chem ; 367: 129846, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399273

RESUMO

The inhibition of α-glucosidase by nine galloyl-based polyphenols with free and unfree galloyl moieties (GMs) was studied. The results show that the inhibitory activity increased with the free GM number increasing. For the compounds with unfree GMs, ellagic acid and hexahydroxydiphenoyl group contributed to the enzyme inhibition. Free GMs could bind not only with the active site of α-glucosidase (competitive inhibition character), but also with the non-active sites (uncompetitive one); however, the former binding interaction was stronger than the latter one. All polyphenols that had inhibitory effects quenched α-glucosidase fluorescence in a static mode through forming a polyphenol-enzyme complex. The number of amino acid residues involved in polyphenol-enzyme binding interactions (hydrogen bonding and π-conjugations) increased with the inhibitory activity increasing. Additionally, two polyphenols with 5 free GMs showing certain hypoglycemic effects in maltose-loading test suggests that GM may be an advisable functional factor for alleviation of type II diabetes symptoms.


Assuntos
Diabetes Mellitus Tipo 2 , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases , Humanos , Simulação de Acoplamento Molecular , Polifenóis
10.
Anal Chem ; 93(46): 15412-15419, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34762397

RESUMO

Designing analytical approaches for enzymatic activity monitoring with high sensitivity and selectivity is of critical value for the diagnosis of diseases and biomedical studies. In this study, we have created a facile one-step synthetic route to prepare orange-red color and yellow fluorescent silicon-containing nanoparticles (Si CNPs) by mixing 3(2-aminoethylamino) propyl (dimethoxymethylsilane) and hydroquinone (HQ) in an aqueous solution. Inspired by the HQ-regulated facile synthetic step and the generation of HQ from α-glucosidase (α-Glu)-catalyzed hydrolysis of 4-hydroxyphenyl-α-d-glucopyranosyl (4-HPαDG), we have designed a straightforward colorimetric and fluorometric α-Glu activity assay using a commercially available 4-HPαDG as the α-Glu substrate. Fluorescent and colorimetric assays for α-Glu activity measurement have been thereby established and exhibited detection limits as low as 0.0032 and 0.0046 U/mL, respectively. Under single excitation at 370 nm, the prepared Si CNPs emitted yellow fluorescence at 520 nm and exhibited an absorbance peak at 390 nm. In addition, the proposed approach reveals various advantages including easy operation, time-saving, and good anti-interference ability. Hence, it could improve the progress of fluorometric and colorimetric enzymatic activity assays with high sensitivity and simplicity. Moreover, the proposed approach was applied for α-Glu inhibitor screening, and its feasibility in real samples was measured by detecting the α-Glu activity in human serum samples.


Assuntos
Colorimetria , Nanopartículas , Corantes Fluorescentes , Humanos , Silício , alfa-Glucosidases
11.
EMBO Mol Med ; 13(11): e14434, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34606154

RESUMO

Pompe disease is a metabolic myopathy due to acid alpha-glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha-glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model and in patients' cells. In cells, stress levels inversely correlated with the ability of rhGAA to correct the enzymatic deficiency. Antioxidants (N-acetylcysteine, idebenone, resveratrol, edaravone) improved alpha-glucosidase activity in rhGAA-treated cells, enhanced enzyme processing, and improved mannose-6-phosphate receptor localization. When co-administered with rhGAA, antioxidants improved alpha-glucosidase activity in tissues from the Pompe disease mouse model. These results indicate that oxidative stress impacts on the efficacy of enzyme replacement therapy in Pompe disease and that manipulation of secondary abnormalities may represent a strategy to improve the efficacy of therapies for this disorder.


Assuntos
Doença de Depósito de Glicogênio Tipo II , Animais , Terapia de Reposição de Enzimas , Glicogênio/metabolismo , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Humanos , Camundongos , Estresse Oxidativo , alfa-Glucosidases/metabolismo , alfa-Glucosidases/uso terapêutico
12.
Molecules ; 26(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34641385

RESUMO

α-Glucosidase was immobilized on magnetic nanoparticles (MNPs) for selective solid-phase extraction of the enzyme's ligands present in Aloe vera, which is a medicinal plant used for the treatment of various diseases and possesses anti-diabetic activity. One new compound, aloeacone (2), together with two known compounds, aloenin aglycone (1) and aloin A (3), were fished out as the enzyme's ligands. The structure of 2 was determined by HR-MS and comprehensive NMR techniques. Compound 3 exhibited a weak inhibitory effect on α-glucosidase, while compounds 1 and 2 were found to possess activation effects on the enzyme for the first time. It is interesting that both an inhibitor and agonists of α-glucosidase were fished out in one experiment.


Assuntos
Enzimas Imobilizadas/metabolismo , Glucosídeos/metabolismo , Nanopartículas de Magnetita/química , Extratos Vegetais/metabolismo , alfa-Glucosidases/metabolismo , Aloe , Catárticos/metabolismo , Emodina/análogos & derivados , Emodina/metabolismo , Enzimas Imobilizadas/química , Glucosídeos/isolamento & purificação , Ligantes , alfa-Glucosidases/química
13.
Braz J Biol ; 83: 00264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34669793

RESUMO

Allium cepa L. is a commonly consumed vegetable that belongs to the Amaryllidaceae family and contains nutrients and antioxidants in ample amounts. In spite of the valuable food applications of onion bulb, its peel and outer fleshy layers are generally regarded as waste and exploration of their nutritional and therapeutic potential is still in progress with a very slow progression rate. The present study was designed with the purpose of doing a comparative analysis of the antioxidant potential of two parts of Allium cepa, i.g., bulb (edible part) and outer fleshy layers and dry peels (inedible part). Moreover, the inhibitory effect of the onion bulb and peel extracts on rat intestinal α-glucosidase and pancreatic α-amylase of porcine was also evaluated. The antioxidant potential of onion peel and bulb extracts were evaluated using 2,2-diphenyl- 1-picryl hydrazyl (DPPH), ferric-reducing antioxidant power assay (FRAP), 2,2'-azino-bis- 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay, H2O2 radical scavenging activity and Fe2+ chelating activity. Total flavonoids and phenolic content of ethanolic extract of onion peel were significantly greater as compared to that of onion bulb. Ethanolic extract of onion peel also presented better antioxidant and free-radical scavenging activity as compared to the ethanolic extract of bulb, while the aqueous extract of bulb presented weakest antioxidative potential. Onion peel extract's α-glucosidase inhibition potential was also correlated with their phenolic and flavonoid contents. The current findings presented onion peel as a possible source of antioxidative agents and phenolic compounds that might be beneficial against development of various common chronic diseases that might have an association with oxidative stress. Besides, outer dry layers and fleshy peels of onion exhibited higher phenolic content and antioxidant activities, compared to the inner bulb. The information obtained by the present study can be useful in promoting the use of vegetable parts other than the edible mesocarp for several future food applications, rather than these being wasted.


Assuntos
Antioxidantes , Cebolas , Animais , Peróxido de Hidrogênio , Extratos Vegetais/farmacologia , Ratos , Suínos , alfa-Glucosidases
14.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639227

RESUMO

Pompe disease (OMIM#232300) is an autosomal recessive lysosomal storage disorder caused by mutations in the GAA gene. According to public mutation databases, more than 679 pathogenic variants have been described in GAA, none of which are associated with mobile genetic elements. In this article, we report a novel molecular genetic cause of Pompe disease, which could be hardly detected using routine molecular genetic analysis. Whole genome sequencing followed by comprehensive functional analysis allowed us to discover and characterize a complex mobile genetic element insertion deep in the intron 15 of the GAA gene in a patient with infantile onset Pompe disease.


Assuntos
Elementos de DNA Transponíveis/genética , Doença de Depósito de Glicogênio Tipo II/patologia , Mutagênese Insercional , alfa-Glucosidases/genética , Criança , Feminino , Doença de Depósito de Glicogênio Tipo II/etiologia , Doença de Depósito de Glicogênio Tipo II/metabolismo , Humanos , Lactente , Masculino , Linhagem , Prognóstico
15.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638570

RESUMO

The microbial biodegradation of new PLA and PCL materials containing birch tar (1-10% v/v) was investigated. Product of dry distillation of birch bark (Betula pendula Roth) was added to polymeric materials to obtain films with antimicrobial properties. The subject of the study was the course of enzymatic degradation of a biodegradable polymer with antibacterial properties. The results show that the type of the material, tar concentration, and the environment influenced the hydrolytic activity of potential biofilm degraders. In the presence of PCL films, the enzyme activities were higher (except for α-D-glucosidase) compared to PLA films. The highest concentration of birch tar (10% v/v) decreased the activity of hydrolases produced by microorganisms to the most significant extent; however, SEM analysis showed the presence of a biofilm even on plastics with the highest tar content. Based on the results of the biological oxygen demand (BOD), the new materials can be classified as biodegradable but, the biodegradation process was less efficient when compared to plastics without the addition of birch tar.


Assuntos
Anti-Infecciosos/química , Betula/química , Plásticos Biodegradáveis/química , Poliésteres/química , Alcatrões/química , Aminopeptidases/metabolismo , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Betula/microbiologia , Plásticos Biodegradáveis/farmacologia , Biofilmes , Análise da Demanda Biológica de Oxigênio , Destilação , Ensaios Enzimáticos , Esterases/metabolismo , Lipase/metabolismo , Casca de Planta/química , Casca de Planta/microbiologia , Poliésteres/metabolismo , Alcatrões/farmacologia , alfa-Glucosidases/metabolismo , beta-Glucosidase/metabolismo
16.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641343

RESUMO

(-)-Epigallocatechin gallate (EGCG), the chief dietary constituent in green tea (Camellia sinensis), is relatively unstable under oxidative conditions. This study evaluated the use of non-thermal dielectric barrier discharge (DBD) plasma to improve the anti-digestive enzyme capacities of EGCG oxidation products. Pure EGCG was dissolved in an aqueous solution and irradiated with DBD plasma for 20, 40, and 60 min. The reactant, irradiated for 60 min, exhibited improved inhibitory properties against α-glucosidase and α-amylase compared with the parent EGCG. The chemical structures of these oxidation products 1-3 from the EGCG, irradiated with the plasma for 60 min, were characterized using spectroscopic methods. Among the oxidation products, EGCG quinone dimer A (1) showed the most potent inhibitory effects toward α-glucosidase and α-amylase with IC50 values of 15.9 ± 0.3 and 18.7 ± 0.3 µM, respectively. These values were significantly higher than that of the positive control, acarbose. Compound 1, which was the most active, was the most abundant in the plasma-irradiated reactant for 60 min according to quantitative high-performance liquid chromatography analysis. These results suggest that the increased biological capacity of EGCG can be attributed to the structural changes to EGCG in H2O, induced by cold plasma irradiation.


Assuntos
Camellia sinensis/química , Catequina/análogos & derivados , Inibidores de Glicosídeo Hidrolases/química , Gases em Plasma/efeitos adversos , alfa-Amilases/antagonistas & inibidores , Animais , Catequina/química , Catequina/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Estrutura Molecular , Oxirredução , Pâncreas/enzimologia , Folhas de Planta/química , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Suínos , Água/química , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
17.
Molecules ; 26(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34684812

RESUMO

It is known that 4F2hc and rBAT are the heavy subunits of the heteromeric amino acid transporters (HATs). These heavy subunits are N-glycosylated proteins, with an N-terminal domain, one transmembrane domain and a bulky extracellular domain (ectodomain) that belongs to the α-amylase family. The heavy subunits are covalently linked to a light subunit from the SLC7 family, which is responsible for the amino acid transport activity, forming a heterodimer. The functions of 4F2hc and rBAT are related mainly to the stability and trafficking of the HATs in the plasma membrane of vertebrates, where they exert the transport activity. Moreover, 4F2hc is a modulator of integrin signaling, has a role in cell fusion and it is overexpressed in some types of cancers. On the other hand, some mutations in rBAT are found to cause the malfunctioning of the b0,+ transport system, leading to cystinuria. The ectodomains of 4F2hc and rBAT share both sequence and structure homology with α-amylase family members. Very recently, cryo-EM has revealed the structure of several HATs, including the ectodomains of rBAT and 4F2hc. Here, we analyze available data on the ectodomains of rBAT and 4Fhc and their relationship with the α-amylase family. The physiological relevance of this relationship remains largely unknown.


Assuntos
Sistemas de Transporte de Aminoácidos/química , alfa-Glucosidases/química , Sequência de Aminoácidos , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos Básicos/química , Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Neutros/química , Sistemas de Transporte de Aminoácidos Neutros/genética , Animais , Domínio Catalítico , Microscopia Crioeletrônica , Cadeia Pesada da Proteína-1 Reguladora de Fusão/química , Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética , Humanos , Modelos Moleculares , Domínios Proteicos , Multimerização Proteica , Subunidades Proteicas , alfa-Glucosidases/genética
18.
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
19.
Biomed Res Int ; 2021: 1585692, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485509

RESUMO

In traditional medicine, various parts of the plant Juglans regia L. are used to treat several pathological conditions including diabetes and infectious and periodontal diseases. This includes the bark of Juglans regia. The present study is aimed at evaluating for the first time the mineral composition, investigating the antidiabetic and antibacterial properties of Moroccan J. regia bark, and finally determining the correlations between the chemical composition of the tested extracts and their biological activities. The mineral composition was determined using inductively coupled plasma atomic emission spectroscopy. Then, nine extracts were prepared by different methods and modalities of extractions and investigated for their antidiabetic activities, via tests of inhibition of alpha-amylase, alpha-glucosidase, and beta-galactosidase enzymes, and for their antibacterial activities against six strains involved in infectious diseases and periodontology. Finally, the correlation between the chemical compositions of the different extracts prepared and their antidiabetic and antibacterial potencies was determined by Principal Component Analysis (PCA). J. regia is an important source of mineral elements, mainly Fe (19849.8), K (3487.8), Mg (2631.03), and P (691.02) mg/kg plant material. All the extracts of J. regia possess antidiabetic activity, and in particular, the macerated acetone extract gave the highest inhibitory activity against alpha-amylase (IC50 value of 5445.33 ± 82.58 µg/mL), alpha-glucosidase (IC50 value of 323.7 ± 1.71 µg/mL), and beta-galactosidase (IC50 value of 811.2 ± 8.32 µg/mL). For the results of antibacterial activity, the macerated acetone extract at the concentration of 80 mg/mL was found to be the most active by inducing inhibition diameters of 12, 17, 18, 11, 14.5, and 16 mm against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Listeria innocua, respectively. PCA allowed us to deduce that the extracts richer in polyphenols, in particular, the two acetone and ethanol macerates, have a better antidiabetic activity against alpha-glucosidase as well as a better antibacterial activity. The results of the present study revealed that the aqueous and organic macerate extracts showed a better antidiabetic activity and justified the use of J. regia bark as an antibacterial and antiseptic agent in traditional Moroccan medicine in the treatment of dental affections.


Assuntos
Juglans/química , Minerais/análise , Casca de Planta/química , Extratos Vegetais/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química , beta-Galactosidase/antagonistas & inibidores , Antibacterianos/farmacologia , Hipoglicemiantes/farmacologia , Técnicas In Vitro , alfa-Glucosidases/metabolismo
20.
Molecules ; 26(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34500797

RESUMO

Despite significant advances in biological and analytical approaches, a comprehensive portrait of the proteome and its dynamic interactions and modifications remains a challenging goal. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to elucidate protein composition, distribution, and relevant physiological and pharmacological functions. Click chemistry focuses on the development of new combinatorial chemical methods for carbon heteroatom bond (C-X-C) synthesis, which have been utilized extensively in the field of chemical proteomics. Click reactions have various advantages including high yield, harmless by-products, and simple reaction conditions, upon which the molecular diversity can be easily and effectively obtained. This paper reviews the application of click chemistry in proteomics from four aspects: (1) activity-based protein profiling, (2) enzyme-inhibitors screening, (3) protein labeling and modifications, and (4) hybrid monolithic column in proteomic analysis.


Assuntos
Inibidores Enzimáticos/farmacologia , Proteoma/análise , Proteômica , Química Click , Ciclo-Oxigenase 2/metabolismo , Inibidores Enzimáticos/química , Estrutura Molecular , N-Acetilglucosaminiltransferases/antagonistas & inibidores , N-Acetilglucosaminiltransferases/metabolismo , Proteínas Quinases/metabolismo , alfa-Glucosidases/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA