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1.
J Chromatogr A ; 1625: 461294, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709337

RESUMO

It is significant to precisely isolate potential active compounds from medicinal herbs containing multiple compounds. Herein, a new strategy for precise separation of lysine-specific demethylase 1 (LSD1) inhibitors from the rhizome of Corydalis yanhusuo (RCY) using counter-current chromatography (CCC) guided by molecular docking and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis was established. First, representative alkaloids from RCY were docked with LSD1 for screening active skeleton compounds. Simultaneously, the crude extract of RCY was preliminarily separated via pH-zone refining CCC. Subsequently, guided by LC-MS/MS analysis of the fragmentation pathways, three potential active fractions were obtained, followed by further online-storage and recycling CCC separation. Finally, three high-purity target quaternary alkaloids compound 3 (dehydrocorydaline), 7 (coptisine), and 8 (columbamine) were successfully isolated as a new class of potential natural LSD1 inhibitors by only one CCC instrument with multiple modes. Compound 3, with the highest LSD1 inhibition ratio of 2.44 µM, was tested for its ability to inhibit tumor invasion and metastasis in U2OS cells. Therefore, the CCC separation guided by virtual screening is a promising method for the targeted isolation of enzyme inhibitors from medicinal herbs.


Assuntos
Corydalis/química , Distribuição Contracorrente/métodos , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/isolamento & purificação , Histona Desmetilases/antagonistas & inibidores , Interface Usuário-Computador , Bioensaio , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/química , Histona Desmetilases/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Simulação de Acoplamento Molecular , Solventes , Espectrometria de Massas em Tandem
2.
PLoS Negl Trop Dis ; 14(5): e0008339, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32437349

RESUMO

Trypanothione reductase (TR) is a key enzyme that catalyzes the reduction of trypanothione, an antioxidant dithiol that protects Trypanosomatid parasites from oxidative stress induced by mammalian host defense systems. TR is considered an attractive target for the development of novel anti-parasitic agents as it is essential for parasite survival but has no close homologue in humans. We report here the identification of spiro-containing derivatives as inhibitors of TR from Trypanosoma brucei (TbTR), the parasite responsible for Human African Trypanosomiasis. The hit series, identified by high throughput screening, was shown to bind TbTR reversibly and to compete with the trypanothione (TS2) substrate. The prototype compound 1 from this series was also found to impede the growth of Trypanosoma brucei parasites in vitro. The X-ray crystal structure of TbTR in complex with compound 1 solved at 1.98 Å allowed the identification of the hydrophobic pocket where the inhibitor binds, placed close to the catalytic histidine (His 461') and lined by Trp21, Val53, Ile106, Tyr110 and Met113. This new inhibitor is specific for TbTR and no activity was detected against the structurally similar human glutathione reductase (hGR). The central spiro scaffold is known to be suitable for brain active compounds in humans thus representing an attractive starting point for the future treatment of the central nervous system stage of T. brucei infections.


Assuntos
Antiprotozoários/farmacologia , Inibidores Enzimáticos/farmacologia , NADH NADPH Oxirredutases/antagonistas & inibidores , Tolueno/análogos & derivados , Trypanosoma brucei brucei/efeitos dos fármacos , Antiprotozoários/isolamento & purificação , Sítios de Ligação , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/isolamento & purificação , Ensaios de Triagem em Larga Escala , NADH NADPH Oxirredutases/química , Ligação Proteica , Conformação Proteica , Tolueno/isolamento & purificação , Tolueno/farmacologia , Trypanosoma brucei brucei/enzimologia
3.
Arch Biochem Biophys ; 687: 108369, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32335047

RESUMO

A neutral tea polysaccharide (TPSN) was isolated from green tea. Gas chromatography analysis showed that TPSN was composed of d-glucose, l-arabinose and d-galactose residues at a molar ratio of 90.0: 9.1: 0.9. The weight-averaged molecular weight of TPSN was determined as about 2.0 × 105 g mol-1 using static light scattering analysis. The result of nuclear magnetic resonance (NMR) spectroscopy indicated that TPSN and water-soluble starch had similar structures. TPSN exhibited inhibitory activity towards α-amylase through the noncompetitive inhibition mechanism, but the tertiary structure of α-amylase related to enzymatic activity, analyzed using circular dichroism spectroscopy, was not affected by TPSN. Meanwhile, TPSN exhibited hydrolysis properties catalyzed by α-amylase. Molecular docking analysis revealed that the various behaviors of TPSN to α-amylase could be attributed to that the different chain segments of TPSN combined with different amino acid residues of α-amylase.


Assuntos
Inibidores Enzimáticos/química , Polissacarídeos/química , Chá/química , alfa-Amilases/antagonistas & inibidores , Animais , Camellia sinensis/química , Ensaios Enzimáticos , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Hidrólise , Cinética , Simulação de Acoplamento Molecular , Peso Molecular , Polissacarídeos/isolamento & purificação , Polissacarídeos/metabolismo , Ligação Proteica , Suínos , alfa-Amilases/metabolismo
4.
J Food Sci ; 85(4): 1060-1069, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32147838

RESUMO

Inonotus obliquus is a traditional mushroom well known for its therapeutic value. In this study, various solvent fractions of I. obliquus were preliminarily screened for their antioxidant, α-amylase and α-glucosidase inhibition properties. To improve the drug delivery, the active fraction (ethyl acetate fraction) of I. obliquus was synthesized into fungisome (ethyl acetate phophotidyl choline complex, EAPC) and its physical parameters were assessed using Fourier transform infrared spectroscopy (FTIR), High performance liquid chromatography (HPLC), Scanning electron microscope (SEM), and ς potential analysis. Then normal human hepatic L02 cells was used to evaluate the cytotoxicity of EAPC. The results showed that EA fraction possesses significant free radical scavenging, α-amylase and α-glucosidase inhibition properties. FTIR, SEM, and HPLC analysis confirmed the fungisome formation. The particle size of EAPC was 102.80 ± 0.42 nm and the ς potential was -54.30 ± 0.61 mV. The percentage of drug entrapment efficiency was 97.13% and the drug release rates of EAPC in simulated gastric fluid and simulated intestinal fluid were 75.04 ± 0.29% and 93.03 ± 0.36%, respectively. EAPC was nontoxic to L02 cells, however it could selectively fight against the H2 O2 induced oxidative damage in L02 cells. This is the first study to provide scientific information to utilize the active fraction of I. obliquus as fungisome. PRACTICAL APPLICATIONS: Inonotus obliquus (IO) is a traditional medicinal fungus. The extracts of IO have obvious antioxidant and hypoglycemic activities. Ethyl acetate (EA) fraction of IO was encapsulated in liposomes to form EAPC. EAPC has a sustained-release effect. It has nontoxic to L02 cells and could protect L02 cells from oxidative damage caused by hydrogen peroxide. This study could provide new ideas for the treatment of diabetes.


Assuntos
Agaricales/química , Antioxidantes/farmacologia , Basidiomycota/química , Inibidores Enzimáticos/farmacologia , Peróxido de Hidrogênio/toxicidade , Extratos Vegetais/farmacologia , alfa-Amilases/antagonistas & inibidores , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , alfa-Amilases/química , alfa-Glucosidases/química
5.
Z Naturforsch C J Biosci ; 75(1-2): 31-39, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32031983

RESUMO

This study aimed to compare the biological activities of 35 herbal hydroethanolic extracts and select high potential extract, which showed antioxidative activity and inhibitory activities of α-glucosidase, lipase, and hyaluronidase, and to investigate the isolation, structural elucidation, and biological activities of five phenolic compounds from the selected extracts of Rosa gallica. On the basis of one-dimensional nuclear magnetic resonance together with the comparison with the literature values, the phenolic compounds were identified as methyl gallate (1), kaempferol-3-O-arabinofuranoside (2), multinoside A acetate (3), kaempferol (4), and quercetin (5), respectively. The results suggest that the extracts from R. gallica show the strongest biological activities in 35 herbal extracts and that 1, 4, and 5 among the five isolated compounds from rose extracts are effective in promoting antioxidative and enzymatic inhibitory activities.


Assuntos
Antioxidantes/química , Fenóis/química , Extratos Vegetais/química , Rosa/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Quempferóis/química , Quempferóis/isolamento & purificação , Espectroscopia de Ressonância Magnética , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Quercetina/química , Quercetina/isolamento & purificação
6.
J Food Sci ; 85(3): 696-706, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32043592

RESUMO

The aim of this study was to extract and purify anthocyanins from Lycium ruthenicum Murr. and evaluate their tyrosinase inhibitory activity. Response surface methodology was devoted to optimize enzyme-assisted extraction of anthocyanins from L. ruthenicum dried fruits. Extraction at 38 °C for 37 min using water-containing pectinase (52.04 mg/100 g dried fruit) rendered an anthocyanin extraction yield of 19.51 ± 0.21 mg/g. The purified anthocyanins were separated from the extract by macroporous resin XDA-6. Antioxidant tests in vitro suggested that the extract and the purified anthocyanins exhibited a potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging capacity, hydroxyl radical scavenging capacity, superoxide radical scavenging capacity, and total reducing power. Thirteen anthocyanins from L. ruthenicum dried fruits were analyzed by HPLC-MS. Moreover, the purified anthocyanins had inhibitory effect on tyrosinase monophenolase (IC50 = 1.483 ± 0.058 mg/mL), and the type of inhibition was competitive inhibition (Ki = 39.83 ± 1.4 mg/mL). The maximum inhibitory activity of the purified anthocyanins (3.00 mg/mL) on tyrosinase diphenolase was 42.16 ± 0.77%, and the type of inhibition was anticompetitive inhibition (Kis = 2.387 ± 0.10 mg/mL). PRACTICAL APPLICATION: The anthocyanins from L. ruthenicum dried fruits can be used as tyrosinase inhibitors in medicine, cosmetics, and food preservation industries.


Assuntos
Antocianinas/química , Inibidores Enzimáticos/química , Lycium/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/química , Antocianinas/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/isolamento & purificação , Frutas/química , Espectrometria de Massas , Monofenol Mono-Oxigenase/química , Oxirredução , Extratos Vegetais/isolamento & purificação
7.
Anal Chim Acta ; 1101: 9-22, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32029123

RESUMO

With a substantial demand for new anti-obesity drugs for the treatment of obesity, screening lipase inhibitors from natural products has become a popular approach toward drug discovery. Due to the significant advantages of excellent reusability, stability and endurance in extreme pH and temperature conditions, lipase immobilization has been employed as a promising strategy to screen lipase inhibitors. Support is a key factor in the process of enzyme immobilization used to provide excellent biocompatibility, stable physical and chemical properties and abundant binding sites for enzymes. Thus, various supports, including nanofibers, polymeric monoliths, mesoporous materials, nanomaterials, membrane and cellulose paper, are systematically introduced and discussed in this review. Considering these supports, the application of the immobilization of lipase in screening compounds from natural products is also comprehensively reviewed, and the outlook for future research directions is described.


Assuntos
Fármacos Antiobesidade/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Enzimas Imobilizadas/química , Lipase/química , Animais , Fármacos Antiobesidade/química , Biocatálise , Burkholderia cepacia/enzimologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Enzimas Imobilizadas/antagonistas & inibidores , Fungos/enzimologia , Lipase/antagonistas & inibidores , Estruturas Metalorgânicas/química , Nanoestruturas/química , Plantas/química
8.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936688

RESUMO

Bioaffinity capturing of molecules allows the discovery of bioactive compounds and decreases the need for various stages in the natural compound isolation process. Despite the high selectivity of this technique, the screening and identification methodology depends on the presence of a protein to capture potential ligands. However, some proteins, such as snake secretory phospholipase A2 (sPLA2), have never been investigated using this approach. The purpose of this study was to evaluate the use of a new method for screening natural compounds using a bioaffinity-guided ultrafiltration method on Crotalus durissus terrificus sPLA2 followed by HPLC-MS to identify the compounds, and this method could be used to discover new anti-inflammatory compounds from the various organisms originating from biodiversity. Different extracts were selected to evaluate their ability to inhibit sPLA2 activity. The extracts were incubated with sPLA2 and the resulting mixture was ultrafiltrated to elute unbound components. The resulting compounds were identified by HPLC-MS. We identified hispidulin as one of the components present in the Moquiniastrum floribundum leaf and evaluated the ability of this isolated compound to neutralize the inflammatory activity of sPLA2 from Crotalus durissus terrificus.


Assuntos
Produtos Biológicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Fosfolipases A2 Secretórias/antagonistas & inibidores , Animais , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cromatografia Líquida de Alta Pressão , Crotalus/genética , Inibidores Enzimáticos/química , Ligantes , Fosfolipases A2 Secretórias/química
9.
Org Lett ; 22(4): 1380-1384, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31999125

RESUMO

(±)-Melipatulinones A-C (1-3), three unique enantiomeric pairs of lignan-phloroglucinol hybrids along with the biogenetically related compound melipatulignan A (4), were isolated from the leaves of Melicope patulinervia. Melipatulinones A (1) and B (2) share a novel spiro[hydrobenzofuran-2,3'-furan] 5/5/6 tricyclic ring system, while melipatulinone C (3) features an unprecedented spiro[cyclopenta[b]hydrofuran-2,3'-furan] 5/5/5 tricyclic framework. Their structures were determined by spectroscopic methods, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Compounds 1-3 exhibited a pancreatic lipase inhibitory effect.


Assuntos
Inibidores Enzimáticos/farmacologia , Lignanas/farmacologia , Lipase/antagonistas & inibidores , Rutaceae/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Lipase/metabolismo , Conformação Molecular , Pâncreas/enzimologia , Folhas de Planta/química , Estereoisomerismo
10.
Microb Pathog ; 140: 103955, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899325

RESUMO

Eleusine coracana (Finger millet) has high nutritional value with numerous health benefits and is of low cost. Isolation of beta-glucan (ßG) from E. coracana (Ec-ßG) has gained increasing research attention. UV-vis spectroscopy used to measure the surface plasmon resonance at 361 nm to confirm the presence of polysaccharides (glucan molecules) in Ec-ßG. X-ray diffraction analysis of Ec-ßG displayed a crystalline nature and confirmed the presence of the ßG molecule. Further, the bioactive compounds of Ec-ßG were screened using gas chromatography-mass spectrometry. The antibacterial activity of Ec-ßG against both Gram-positive (Lysinibacillus fusiformis, Enterococcus faecalis) and Gram-negative (Proteus vulgaris, Shigella sonnei) bacteria were assessed through minimum inhibitory concentrations <70 µg/ml of Ec-ßG. In addition, the antibiofilm activity and bacterial viability of Ec-ßG at 100 µg/ml was confirmed by light and confocal laser scanning microscopy. Furthermore, Ec-ßG inhibits α-amylase and α-glucosidase at an IC50 -value of 1.23 and 1.42 µg/ml, respectively. Superoxide anion scavenging activity at IC50-1.4 µg/ml and DPPH radical scavenging activity at IC50-1.2 µg/ml showed that Ec-ßG had potential antioxidant property. The in vitro hemolysis assay for biocompatibility of Ec-ßG at 200 µg/ml showed 0.06 ± 0.09%. Therefore, Ec-ßG has the potential to act as a suggestive agent for antibacterial, antidiabetic, and antioxidant activity.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Biofilmes/efeitos dos fármacos , Eleusine/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , beta-Glucanas/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/fisiologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Shigella sonnei/efeitos dos fármacos , Shigella sonnei/fisiologia , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , beta-Glucanas/química , beta-Glucanas/isolamento & purificação
11.
Phytochemistry ; 170: 112181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31727321

RESUMO

Gymnema sylvestre (Retz.) R. Br. ex Schult. has a long history to be used as an antidiabetic herbal medicine. Various varieties of G. sylvestre, have been studied intensively on their 3ß-hydroxy oleanane triterpenoid composition for hypoglycemic effects. It is also well-known that most species belonging to the same genus have similar chemical composition and biological activity. Thus, an extract of the Gymnema latifolium Wall. ex Wight, which showed considerable protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (>70% inhibition at 30 µg/mL), was studied intensively. Extensive chemical investigation on the 70% EtOH of G. latifolium led to the isolation of four previously undescribed oleanane hemiacetal glycosides, gymlatinosides GL1-GL4, three previously undescribed oleanane glycosides, gymlatinosides GL5-GL7, and two known 3ß-hydroxy oleanane analogs. The structures of the previously undescribed compounds were elucidated using diverse spectroscopic methods. The hemiacetal structure of the glycoside portion was further elaborated precisely by HMBC and J resolved proton NMR. Gymlatinosides GL2 and GL3 showed considerable PTP1B inhibitory effect.


Assuntos
Inibidores Enzimáticos/farmacologia , Glicosídeos/farmacologia , Gymnema/química , Ácido Oleanólico/análogos & derivados , Compostos Fitoquímicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
12.
Phytochemistry ; 170: 112224, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812919

RESUMO

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


Assuntos
Aspergillus/química , Benzopiranos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Pigmentos Biológicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Benzopiranos/química , Benzopiranos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Pigmentos Biológicos/química , Pigmentos Biológicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade
13.
Nat Prod Res ; 34(4): 558-562, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30388891

RESUMO

Methanol extract of Indigofera hirsuta, was evaluated for its antiradical potential and capacity in inhibiting lipoxygenase and aldose/aldehyde reductase enzymes. The ethyl acetate fraction derived from the methanol extract partition, showed the greatest antioxidant capacity, while the butanol was the strongest inhibitor of lipoxygenase enzyme. All fractions (diethyl ether, ethyl acetate, butanol and the aqueous residue) exhibited strong inhibition capacity of both aldose/aldehyde reductase enzymes, which comes in agreement with the ethnomedicinal plant utilization as an antidiabetic agent. LC-DAD-MS(ESI+) fraction analysis verified the findings above, leading to a conclusion regarding the biological activities attributed to the main compounds. Phytochemical analysis led to the identification of an indolic dimer, cinnamic acids, phenolics, flavonoid glycosides, a cyclic polyol, the rare sugar 1-methyl-ß-D-glucopyranoside and glycerol. Many of these compounds were isolated for the first time in Indigofera species while the indolic dimer was isolated for the first time in the Fabaceae family.


Assuntos
Antioxidantes/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Indigofera/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Aldeído Redutase/antagonistas & inibidores , Antioxidantes/química , Antioxidantes/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Flavonoides/análise , Glicosídeos/análise , Humanos , Inibidores de Lipoxigenase , Fenóis/análise , Fenóis/química , Compostos Fitoquímicos/isolamento & purificação , Componentes Aéreos da Planta/química
14.
Nat Prod Res ; 34(5): 675-682, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30445849

RESUMO

In the course of our continuing investigation of bioactive secondary metabolites from marine-derived fungal strains, a racemate of a novel diphenolic derivative named (±)-tylopilusin D (1) along with ten previously known secondary metabolites (2-11) were isolated from a marine-derived fungal strain Aspergillus sp. SF-5929. Their structures were elucidated mainly by analysis of NMR and MS data. In addition, the inhibitory effects of the isolated compounds against protein tyrosine phosphatase 1B (PTP1B) activity were evaluated, and compounds 1, 2, and 5-7 inhibited PTP1B activity with IC50 values ranging from 3.3 to 8.1 µM. Kinetics studies suggested that compounds 1, 2, and 5 had noncompetitive inhibitory effects against PTP1B.


Assuntos
Aspergillus/química , Inibidores Enzimáticos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Concentração Inibidora 50 , Cinética , Estrutura Molecular , Análise Espectral
15.
Nat Prod Res ; 34(4): 553-557, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30317858

RESUMO

Urease inhibition potential of compound (1), guaiane-type sesquiterpene (2), confertin (3) and scopoletin (4) was carried out with high throughout mechanism-based assay. These compounds were isolated from Hypochaeris radicata L., an Asteraceae family member. The pure compounds were screened for their urease and carbonic anhydrase inhibitory activities. The ethyl acetate fractions were subjected to column chromatography, which resulted in the isolation and purification of four compounds (1-4). On evaluation, compounds (1-4) exhibited selective activity against urease enzyme with an IC50 value of 180.11 ± 2.00, 27.18 ± 0.80, 24.12 ± 0.2 and 30.12 ± 1.10 µM respectively. The compounds (1-4) were found to be inactive against carbonic anhydrase enzyme. Thiourea was used as standard inhibitor (21 ± 0.14 µM) of urease enzyme.


Assuntos
Asteraceae/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Urease/antagonistas & inibidores , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/análise , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
16.
J Chromatogr A ; 1615: 460711, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31759638

RESUMO

With the increasing demand for lipase inhibitors and new drugs used in the clinical treatment of obesity, it is of great significance to screen lipase inhibitors from traditional Chinese medicines (TCMs) via capillary electrophoresis. In this work, Fe3O4@TiO2 nanoparticles was fabricated by solvothermal method and employed as an improved magnetic support to immobilize lipase through electrostatic interaction. By the method of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffraction, the magnetic nanoparticles were characterized. The immobilized enzyme possessed advantages of a wider range for pH and temperature endurance, better storage stability and reusability. The kinetics performances of the immobilized lipase were studied. When p-Nitrophenyl palmitate (pNPP) was used as enzyme substrate, the Michaelis-Menten constant was calculated to be 2.51 mM and its inhibition constant for Orlistat was ascertained to be 13.41 µM. Ultimately, the established method was applied to lipase inhibitors screening from 6 Tibetan medicines with lipase inhibitory activity and Oxytropis falcate Bunge was screened out for its supreme lipase inhibitory activity. 11 compounds in the Oxytropis falcate Bunge were further screened, five compounds exhibited similar inhibitory activity to Orlistat, and one compound (kaempferol) presented better inhibitory activity than Orlistat, which is the most commonly used drugs to treat obesity in clinic. This work not only developed a method for new anti-obesity drugs discovery, but also provided inspiration for exploring new medicinal value of the TCMs.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/isolamento & purificação , Lipase/antagonistas & inibidores , Medicina Tradicional Chinesa , Eletroforese Capilar , Enzimas Imobilizadas/química , Concentração de Íons de Hidrogênio , Ferro/química , Cinética , Magnetismo , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Tibet , Titânio/química , Difração de Raios X
17.
Food Chem ; 305: 125506, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606690

RESUMO

Grapes are known to contain high quantity of polyphenolic compounds, including caffeic, coumaric and ferulic acids esterified with tartaric acid, to yield caftaric, coutaric and fertaric acids, respectively. These acids are more abundant in unripe grapes, which can be processed into verjuice, a product that shows intrinsic resistance against microbial growth and significant antioxidant activity. In the present work, the isolation of hydroxycinnamoyl tartaric acids from unripe grape juice by chromatographic techniques was described. Moreover, the capability of caftaric acid to inhibit tyrosinase activity was evaluated by spectrophotometric assays. According to the kinetics parameters calculated, caftaric acid was shown to be a competitive inhibitor of tyrosinase, more potent than the related caffeic and chlorogenic acids, suggesting that it can be used in cosmetic and food industries for the development of natural skin whitening formulations and as an agent able to counteract the enzymatic browning of food.


Assuntos
Sucos de Frutas e Vegetais/análise , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Espectrofotometria , Vitis/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia
18.
Curr Top Med Chem ; 20(2): 111-120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31854280

RESUMO

BACKGROUND: Neuraminidase inhibitors (NAIs) are the only class of antivirals in clinical use against influenza virus approved worldwide. However, approximately 1-3% of circulating strains present resistance mutations to oseltamivir (OST), the most used NAI. Therefore, it is important to catalogue new molecules to inhibit influenza virus, especially OST-resistant strains. Natural products from tropical plants used for human consumption represent a worthy class of substances. Their use could be stimulated in resource-limited setting where the access to expensive antiviral therapies is restricted. METHODS: We evaluated the anti-influenza virus activity of agathisflavone derived from Anacardium occidentale L. RESULTS: The neuraminidase (NA) activity of wild-type and OST-resistant influenza virus was inhibited by agathisflavone, with IC50 values ranging from 20 to 2.0 µM, respectively. Agathisflavone inhibited influenza virus replication with EC50 of 1.3 µM. Sequential passages of the virus in the presence of agathisflavone revealed the emergence of mutation R249S, A250S and R253Q in the NA gene. These changes are outside the OST binding region, meaning that agathisflavone targets this viral enzyme at a region different than conventional NAIs. CONCLUSION: Altogether our data suggest that agathisflavone has a promising chemical structure for the development of anti-influenza drugs.


Assuntos
Anacardium/química , Biflavonoides/farmacologia , Inibidores Enzimáticos/farmacologia , Neuraminidase/antagonistas & inibidores , Orthomyxoviridae/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Animais , Biflavonoides/química , Biflavonoides/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Madin Darby de Rim Canino/efeitos dos fármacos , Células Madin Darby de Rim Canino/virologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Neuraminidase/metabolismo , Orthomyxoviridae/enzimologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
19.
Food Chem ; 309: 125742, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704068

RESUMO

Extracts from the edible insects Acheta domesticus and Tenebrio molitor were obtained by ultrasound-assisted extraction (UAE) and pressurized-liquid extraction (PLE) using ethanol (E) or ethanol:water (E:W). Characterization by GC-MS was performed and total phenolic compounds (TPC), antioxidant activity (DPPH) and pancreatic lipase inhibitory capacity were assayed. Most extracts, mainly ethanolic extracts, predominantly presented lipids as free fatty acids, followed by aminoacids, organic acids, carbohydrates, hydrocarbons and sterols. The UAE-E:W extracts were different, being characterized by organic acids for A. domesticus, or aminoacids for T. molitor. All the extracts exhibited antioxidant activity, which correlated with TPC values, being the E:W extracts the most effective. All the extracts showed inhibitory activity of lipase, although those from T. molitor and extracted by PLE were the most effective. Therefore, bioactive insect extracts can be selectively obtained by advanced methods of extraction, being aqueous ethanol preferred for antioxidant activity and PLE for inhibitory lipase activity.


Assuntos
Antioxidantes/química , Inibidores Enzimáticos/química , Gryllidae/química , Lipase/antagonistas & inibidores , Tenebrio/química , Animais , Antioxidantes/isolamento & purificação , Insetos Comestíveis/química , Inibidores Enzimáticos/isolamento & purificação , Lipase/química
20.
Talanta ; 206: 120195, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514831

RESUMO

The ability to separate bioactive compounds from herbal medicines, which contain abundant components, is crucial for drug discovery. Conventional Countercurrent chromatography (CCC) methods for separating bioactive compounds are labor intensive and show low efficiency. Here, we present a novel integrative CCC method for separating lysine-specific demethylase 1 (LSD1) inhibitors from the roots of Salvia miltiorrhiza (RSM). The methanol extracts of RSM were separated into hydrosoluble and liposoluble fractions, which were online stored in coils. Subsequently, the targeting LSD1 constituents were isolated using isocratic, gradient, or recycling elution mode. All separation processes could be accomplished using one CCC apparatus. Using our separation strategy, two phenylpropanoids and four tanshinones were isolated, which were determined to be new classes of natural LSD1 inhibitors. Salvianolic acid B, which showed the most potent inhibitory activity with an IC50 of 0.11 µM, exhibiting a considerable potential as an anticancer agent. Promisingly, the integrative CCC could be a crucial tool for the target separation of enzyme inhibitors from herbal medicines.


Assuntos
Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Raízes de Plantas/química , Salvia miltiorrhiza/química , Benzofuranos/isolamento & purificação , Benzofuranos/metabolismo , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cinamatos/isolamento & purificação , Cinamatos/metabolismo , Cinamatos/farmacologia , Distribuição Contracorrente/métodos , Depsídeos/isolamento & purificação , Depsídeos/metabolismo , Depsídeos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Histona Desmetilases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Fenantrenos/isolamento & purificação , Fenantrenos/metabolismo , Fenantrenos/farmacologia , Ligação Proteica
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