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1.
J Chromatogr A ; 1616: 460774, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31937408

RESUMO

Bananas and plantains (Musa spp.) are used as nutritious foods, and at the same time, are a source of phytoconstituents for the pharmaceutical industry. As biological activities of especially the pulp and peel of Musa spp. have been documented, this study investigated the variation in the secondary metabolite profiles of the leaves from field, in vitro-grown and acclimatized accessions. The genetic fidelity of the diverse accessions was assessed using diversity array technology sequencing. It showed that the in vitro-grown accessions were true-to-type with the field samples. The antioxidant and anticholinesterase activities of the samples from different culture systems (field and in vitro) were evaluated by UV-spectrophotometry and compared to high-performance thin-layer chromatography-effect-directed analysis (HPTLC-EDA). The latter was applied for the first time for effect-directed profiling of the polar and medium polar sample components via different biochemical and biological assays. Compound zones showed acetyl-/butylrylcholinesterase inhibition (zones 1-4), α-/ß-glucosidase inhibition (zones 1 and 2) as well as antioxidative (zones 1-3) and antimicrobial (zone 4) activities. Structures were preliminary assigned by HPTLC-HRMS. The HPTLC was effective for bioactivity-guided characterization of the bioactive constituents in Musa spp. accessions. Accumulation of useful metabolites, especially compounds with antioxidant and anticholinesterase properties, was higher in samples from in vitro system. This validated the use of plant tissue culturing as an alternative method for large scale production of plant material and supply of bioactive constituents.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia em Camada Delgada , Espectrometria de Massas , Musa/química , Anti-Infecciosos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Técnicas de Química Analítica/instrumentação , Inibidores da Colinesterase/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Musa/crescimento & desenvolvimento
2.
Nat Prod Res ; 34(4): 549-552, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30445826

RESUMO

The aim of this study was to determine, for the first time, the chemical composition of Peltigera horizontalis thallus and apothecia extracts (ether, ethyl acetate, dichloromethane and acetone) by HPLC-UV and GC-MS, and evaluate activity of genotoxic, anticholinesterase, antioxidant and antibacterial potential of acetone extracts. Major constituents of thallus extracts were gyrophoric acid, and methyl gyrophorate while dominant component of apothecia extracts was tenuiorin. The predominant volatile compounds in extracts were methyl orsellinate, dodecyl acrylate, orcinol and orcinol monomethyl ether. The thallus acetone extract at concentration of 2.0 µg mL-1 gave the greatest decrease in the micronuclei frequency (22.4%) of all tested extracts. Apothecia extract showed stronger antioxidant activity as compared to thallus extract. Tested extracts at concentration of 10 mg mL-1 exhibited inhibitory effect (16.5% for thallus and 12.8% for apothecia) on pooled human serum cholinesterase. P. horizontalis acetone extracts had no activity against the tested five bacteria strains.


Assuntos
Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Ascomicetos/química , Inibidores da Colinesterase/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Extratos Vegetais/química , Resorcinóis/análise
3.
Nat Prod Res ; 34(6): 816-822, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30398365

RESUMO

The chemical constituents of Cupressus macrocarpa were investigated. A new neolignan glycoside (1) in addition to nine known compounds were isolated. The acetylcholinesterase (AChE) inhibitory activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of different fractions and isolates of C. macrocarpa were evaluated. The light petroleum fraction showed the highest activity in both assays with IC50 value of 88.79 µg/ml and 152.58 µg/ml for the AChE inhibitory activity and MRSA antibacterial activities, respectively. Weak to moderate activity were detected for the isolated compounds.


Assuntos
Antibacterianos/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Cupressus/química , Antibacterianos/farmacologia , Inibidores da Colinesterase/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química
4.
Chem Biodivers ; 17(1): e1900600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793197

RESUMO

Four new hetisine-type C20 -diterpenoid alkaloids, named as coreanines A-D (1-4), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids (5-17). Their structures were elucidated by extensive spectroscopic methods including IR, HR-ESI-MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity.


Assuntos
Acetilcolinesterase/metabolismo , Aconitum/química , Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Diterpenos/farmacologia , Raízes de Plantas/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Electrophorus , Estrutura Molecular
5.
Nat Prod Res ; 34(3): 425-428, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30450961

RESUMO

Phytochemical investigation of Illicium micranthum led to the isolation of two new prenylated C6-C3 compounds, 12-O-methyl-2,3-dehydroillifunone C (1) and illiciminone A (2), together with three known analogues (3-5) and one known sesquiterpene lactone (6). The structures were established by extensive spectroscopic characterization and the reported data. All the isolates were evaluated for their acetylcholinesterase (AChE) inhibition activity. Compound 5 showed weak inhibitory activity (46.0%) at 50 µM concentration.


Assuntos
Illicium/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Prenilação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Análise Espectral
6.
J Pharm Biomed Anal ; 177: 112840, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31522096

RESUMO

Alzheimer's disease (AD) is the most widespread neurodegenerative disease; there are around ten million new cases of Alzheimer yearly worldwide especially in middle or low-income countries. Pistacia is a genus of flowering plants including the well-known, economically important P. chinensis Bunge, P. lentiscus L. and P. khinjuk. In this study, the metabolic profiling of Pistacia leaves extracts was achieved via UHPLC-ESI-MS analysis and GC-MS analysis employing chemometric analysis for their discrimination. In addition, the methanolic extracts of different Pistacia species were assessed for their anti-cholinesterase and anti-inflammatory activities by various in vitro assays. 37 and 30 metabolites belonging to different classes were identified by UHPLC-ESI-MS and GC-MS analyses respectively. Chemometric analysis revealed that P. lentiscus and P. khinjuk were more closely related chemically to each other. All studied Pistacia leaves extracts showed apparent anti-cholinesterase and anti-inflammatory activities, which promotes their use in the prevention and management of AD.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Memória/efeitos dos fármacos , Pistacia/química , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Ensaios Enzimáticos , Eritrócitos , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Voluntários Saudáveis , Hemólise/efeitos dos fármacos , Humanos , Metabolômica/métodos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Pistacia/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Folhas de Planta/metabolismo , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos
7.
Fitoterapia ; 139: 104378, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31676395

RESUMO

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525 ±â€¯0.140 µM, which was comparable with the positive control, huperzine A (IC50 = 0.143 ±â€¯0.029 µM).


Assuntos
Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Lycopodiaceae/química , Alcaloides/isolamento & purificação , China , Inibidores da Colinesterase/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Raízes de Plantas/química
8.
BMC Complement Altern Med ; 19(1): 296, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694704

RESUMO

BACKGROUND: Bergenia ciliata is a medicinal plant used for the treatment of diarrhea, vomiting, fever, cough, diabetes, cancer, pulmonary disorders and wound healing. METHODS: In this study, Bergenia ciliata crude extract, subfractions, and isolated compounds were evaluated for their antioxidant and anticholinesterase potential. The free radical scavenging capacities of the extracts determined using DPPH and ABTS assays. The anticholinesterase potentials were determined using acetylcholine esterase and butyryl choline esterase enzymes. To determine the phytochemical composition, the extracts were subjected to HPLC analysis and silica gel column isolation. Based on HPLC fingerprinting results, the ethyl acetate fraction was found to have more bioactive compounds and was therefore subjected to silica gel column isolation. As a result, three compounds; pyrogallol, rutin, and morin were isolated in the pure state. The structures of the isolated compounds were elucidated using spectroscopic techniques like 1H-NMR, IR and UV-Visible. RESULTS: The crude extract showed maximum anticholinesterase (acetylcholinesterase = 90.22 ± 1.15% and butyrylcholinesterase = 88.22 ± 0.71%) and free radical scavenging (87.37 ± 2.45 and 83.50 ± 0.70% respectively against DPPH and ABTS radicals) potentials. The total phenolic contents (expressed as equivalent of gallic acid; mgGAE/g) were higher in ethyl acetate fraction (80.96 ± 1.74) followed by crude extract (70.65 ± 0.86) while the flavonoid contents (expressed as quercetin equivalent; mgQE/g) and were higher in crude extract (88.40 ± 1.12) followed by n-butanol fraction (60.10 ± 1.86). The isolated bioactive compounds pyrogallol, rutin, and morin were found active against ABTS and DPPH free radicals. Amongst them, pyrogallol was more active against both free radicals. Reasonable anticholinesterase activities were recorded for pyrogallol against selected enzymes. CONCLUSION: The extracts and isolated compounds showed antioxidant and acetylcholinesterase inhibitory potentials. It was concluded that this plant could be helpful in the treatment of oxidative stress and neurological disorders if used in the form of extracts.


Assuntos
Antioxidantes/química , Inibidores da Colinesterase/química , Extratos Vegetais/química , Saxifragaceae/química , Acetilcolinesterase/química , Antioxidantes/isolamento & purificação , Butirilcolinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Rizoma/química
9.
Int J Med Mushrooms ; 21(8): 755-763, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679283

RESUMO

The involvement of high acetylcholinesterase (AChE) activity and oxidative stress in the brain is well documented in the progression of dementia. Thus, finding a drug with both AChE-inhibitory and antioxidant activities could be beneficial in treating dementia. We previously reported the AChE-inhibitory and antioxidant-mediated antiamnestic effects of a hydromethanol extract from Ganoderma mediosinense (HME), which we evaluated using in vitro and in vivo models. Mycochemical screening of HME showed the presence of phenols. Building on those findings, this study was designed to isolate the compound responsible for the AChE-inhibitory and antioxidant activities of G. mediosinense. The HME was fractionated sequentially with solvents-namely, hexane, chloroform, and ethyl acetate. The prepared fractions were evaluated by using Ellman and DPPH-inhibitory assays in vitro. Among the fractions, the ethyl acetate fraction showed appreciable AChE-inhibitory (half-maximal inhibitory concentration [IC50] 0.81 ± 0.04 mg/mL) and DPPH scavenging (IC50 2.04 ± 0.77 µg/mL) activities; therefore it was subjected to flash chromatography, which separated 9 subfractions. Subfraction 7 showed marked activity in inhibiting AChE (IC50 0.10 ± 0.02 mg/mL) and free radicals (IC50 1.22 ± 0.04 µg/mL). Purification of subfraction 7 yielded a white compound, AK1. This was characterized as gallic acid by using Fourier-transform infrared, nuclear magnetic resonance, and mass spectral studies. This study shows that gallic acid, a well-recognized phenolic acid, is responsible for the AChE-inhibitory and DPPH scavenging activities of G. mediosinense.


Assuntos
Acetilcolinesterase/metabolismo , Antioxidantes/metabolismo , Inibidores da Colinesterase/isolamento & purificação , Demência/tratamento farmacológico , Ácido Gálico/isolamento & purificação , Ganoderma/química , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Radicais Livres/metabolismo , Ácido Gálico/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos
10.
Molecules ; 24(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752124

RESUMO

Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 µg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 µg/mL, respectively) as compared to gallic acid and the tool compound "galantamine hydrobromide" (IC50 7.89 and 1.45 µg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with π-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.


Assuntos
Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Sinergismo Farmacológico , Humanos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Tinospora/química
11.
Fitoterapia ; 139: 104375, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629050

RESUMO

Picrasamide A (1), a new cinnamamide derivative, together with two new ß-carboline alkaloids (2 and 3) and five known ß-carboline alkaloids (4-8) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated by detailed analyses of UV, IR, HRESIMS, and NMR data. Compound 1 was the first case of cinnamamide derivative from genus Picrasma. The AChE inhibitory activity and the antimicrobial activity of 1-8 were assessed. In addition, preliminary structure-activity relationships of these ß-carboline alkaloids on the AChE inhibitory activity and antimicrobial activity were proposed.


Assuntos
Antibacterianos/farmacologia , Inibidores da Colinesterase/farmacologia , Cinamatos/farmacologia , Picrasma/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Carbolinas/isolamento & purificação , Carbolinas/farmacologia , China , Inibidores da Colinesterase/isolamento & purificação , Cinamatos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Relação Estrutura-Atividade
12.
Molecules ; 24(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597363

RESUMO

Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman's Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.


Assuntos
Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Kadsura/química , Caules de Planta/química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Ativação Enzimática/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
13.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3213-3220, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602874

RESUMO

A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg·L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg·L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.


Assuntos
Ascomicetos/química , Ascomicetos/classificação , Huperzia/microbiologia , Acetilcolinesterase , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ascomicetos/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/metabolismo , Endófitos/classificação , Endófitos/isolamento & purificação , Camundongos , Células RAW 264.7
14.
Fitoterapia ; 139: 104366, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629868

RESUMO

Phytochemical investigation of the ethyl acetate extract of Lycopodiastrum casuarinoides (Spring) Holub (Lycopodiaceae) led to the isolation of nine compounds, including two new serratene triterpenoids, serrat-14-en-3α,21α-diol (1), 26-nor-8-oxo-21-one-α-onocerin (6), one new abietane diterpenoid, lycocasuarinone A (7), one new sesquiterpene acid, 7, 9-diene-1,4-epoxy-2-hydroxy-10-carboxylic acid (8) and one new chromone derivative, 5,7-dihydroxy-2-methyl esterchromone (9), together with four known serratene triterpenoids (2-5). Abietane diterpenoid (7) and sesquiterpene acid (8) from Lycopodiastrum casuarinoides are reported for the first time. Their structures and stereochemistry were unambiguously elucidated by spectroscopic analysis and comparison with known ones. All the compounds were tested for acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. Bioactivity assays revealed that compound 6 exhibited the most potent AChE inhibitory effect.


Assuntos
Abietanos/farmacologia , Inibidores da Colinesterase/farmacologia , Lycopodiaceae/química , Sesquiterpenos/farmacologia , Triterpenos/farmacologia , Abietanos/isolamento & purificação , China , Inibidores da Colinesterase/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos/isolamento & purificação , Triterpenos/isolamento & purificação
15.
Comput Biol Chem ; 83: 107129, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606587

RESUMO

In vitro acetylcholinesterase activities of the hexane, dichloromethane, ethyl acetate, n-butanol and aqueous extracts of leaves of Ocotea percoriacea Kosterm. (Lauraceae) were evaluated. The bioguided fractionation of the most active extract (dichloromethane) using silica gel open-column chromatography led to an active alkaloidal fraction composed of isocorydine N-oxide, isocorydine N-oxide derivative, palmatine, roemerine and roemerine N-Oxide. The identification of the chemical structure of these compounds was carried out with high-performance liquid chromatography coupled to electrospray ionization multiple-stage mass spectrometry (HPLC-ESI-MS/MS). Aiming to understand their inhibitory activities, these alkaloids were docked into a 3D model of Electrophorus electricus Acetylcholinesterase (EelAChE) built in the Modeller 9.18 employing homology modeling approach. The results suggest that the alkaloids had the same binding mode and, possibly, the inhibition mechanism of classic drugs (ex. tacrine and donepezil). The structural difference of these compounds opens a new opportunity for the optimization of leading compounds.


Assuntos
Acetilcolinesterase/metabolismo , Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Modelos Moleculares , Ocotea/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Electrophorus , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Espectrometria de Massas em Tandem
16.
Phytochemistry ; 168: 112128, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557705

RESUMO

The isolation of bioactive compounds from natural sources is a key step in drug discovery and development, however, this procedure is usually expensive and difficult due to the complexity and the limited amounts of the metabolites in the extracts. Thus, rational or targeting isolations are becoming more popular to reduce the bottlenecks in bioactive natural products research. In this study, we used a LC-MS-based metabolomic approach and biochemometric statistical tools (PCA and OPLS-DA) to identify potential anti-cholinesterase alkaloids predictors in Zanthoxylum genus (Rutaceae). For this purpose, 41 alkaloid extracts from nine Colombian Zanthoxylum species were screened by UHPLC-UV-HRMS and inhibitory activity against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE). Based on the screening results, a multivariate statistical analysis (MVA) and selection of anti-cholinesterase candidates were performed using the S-plot from the OPLS-DA model. The supervised analysis (OPLS-DA) paring the anti-cholinesterase screening and LC-HRMS data showed at least 11 ChE inhibition markers which could have contributed in the differentiation of active and inactive extracts. The predictors were tentatively identified by comparing chromatographic retention times (Rt) and accurate mass and MS2 fragmentation patterns. In general, the inhibition markers correspond to four types of isoquinoline alkaloids: tetrahydroprotoberberines, protoberberines, dihydrobenzophenanthridines and benzophenanthridines. The most active extracts from Z. schreberi and Z. monophylum showed the highest presence of berberine and chelerythrine, previously reported as cholinesterase inhibitors. Thus, to validate the results of the OPLS-DA model, three alkaloids from the bark of Z. schreberi (identified as berberine, chelerythrine and columbamine) were bio-directed isolated, and all of them showed strong inhibition against both enzymes. These findings support our statistical models and contribute to the rational search of anticholinesterase alkaloids. Therefore, LC-MS-based metabolomic approach combined with chemometric statistical analysis are shown as useful tools for the isolation of targeted bioactive natural products, contributing to improve the research and development stages of lead compounds.


Assuntos
Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Zanthoxylum/metabolismo , Acetilcolinesterase/metabolismo , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Relação Dose-Resposta a Droga , Electrophorus , Cavalos , Estrutura Molecular , Casca de Planta/química , Casca de Planta/metabolismo , Especificidade da Espécie , Relação Estrutura-Atividade , Zanthoxylum/química
17.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426402

RESUMO

Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids-teucdiol C (1), D (2), E (3), and F (4), together with two known sesquiterpenoids teucdiol B (5) and epi-guaidiol A (6)-were obtained from its fermented broth of T. albuminosus. Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction. Epi-guaidiol A showed obvious anti-acetylcholinesterase activity in a dose-dependent manner. The experimental results displayed that T. albuminosus possess the pharmaceutical potential for Alzheimer's disease, and it was an effective way to dig new pharmaceutical agent of T. albuminosus with the microbial fermentation technique.


Assuntos
Inibidores da Colinesterase/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Termitomyces/química , Doença de Alzheimer/tratamento farmacológico , Animais , Fermentação , Humanos , Isópteros/fisiologia , Espectroscopia de Ressonância Magnética , Sesquiterpenos/química , Sesquiterpenos/classificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Simbiose , Termitomyces/metabolismo , Termitomyces/fisiologia
18.
Chem Biodivers ; 16(10): e1900341, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31465610

RESUMO

The aim of this work was to investigate the enzyme inhibition, antioxidant activity, and phenolic compounds of Lecokia cretica (Lam.) DC. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase enzymes were strongly inhibited by the L. cretica extracts. IC50 values for the three enzymes were found as 3.21 mg/mL, 2.1 mg/mL, and 2.07 mg/mL, respectively. Antioxidant activities were examined in both aqueous and ethanol (EtOH) extracts using CUPRAC, FRAP, and DPPH method. Also, the phenolic compounds of the endemic plant were identified and quantified by using HPLC/MS/MS. According to the results, the extracts have remarkable antioxidant activities. The most abundant phenolic acids of L. cretica in EtOH extract were determined as quinic acid (12.76 mg/kg of crude extract), chlorogenic acid (3.39 mg/kg), and malic acid (2.38 mg/kg).


Assuntos
Antioxidantes/farmacologia , Antagonistas Colinérgicos/farmacologia , Hipoglicemiantes/farmacologia , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Antioxidantes/química , Antioxidantes/isolamento & purificação , Apiaceae/química , Butirilcolinesterase/metabolismo , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeo Hidrolases/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
19.
Phytochemistry ; 165: 112055, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31261031

RESUMO

Twenty-one known Amaryllidaceae alkaloids of various structural types and one undescribed alkaloid, named narcimatuline, have been isolated from fresh bulbs of Narcissus pseudonarcissus L. cv. Dutch Master. The chemical structures were elucidated by combination of MS, HRMS, 1D and 2D NMR spectroscopic techniques, and by comparison with literature data. Narcimatuline amalgamates two basic scaffolds of Amaryllidaceae alkaloids in its core, namely galanthamine and galanthindole. All isolated compounds were evaluated for their in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), prolyl oligopeptidase (POP), and glycogen synthase kinase-3ß (GSK-3ß) inhibitory activities. The most interesting biological profile was demonstrated by newly isolated alkaloid narcimatuline.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Alcaloides de Amaryllidaceae/farmacologia , Inibidores da Colinesterase/farmacologia , Narcissus/química , Fármacos Neuroprotetores/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Relação Dose-Resposta a Droga , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Serina Endopeptidases/metabolismo , Relação Estrutura-Atividade
20.
Fitoterapia ; 137: 104277, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351127

RESUMO

Five new Lycopodium alkaloids, huperzine Y1 (1), huperzine Y2 (2), huperzine Y3 (3), (+)-huperzine Z (4a) and (-)-huperzine Z (4b) as well as ten known alkaloids (5-14) were isolated from Huperzia serrata. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 4a and 4b were a pair of enantiomers successfully separated by chiral HPLC resolution. Compounds 2 and 3 indicated inhibitory activities against acetylcholinesterase with IC50 value of 57.1 ±â€¯1.6 and 32.7 ±â€¯1.0 µΜ, respectively. However, no compound showed inhibitory effect on butyrocholinesterase at the concentration of 100 µΜ.


Assuntos
Alcaloides/farmacologia , Huperzia/química , Acetilcolinesterase , Alcaloides/isolamento & purificação , Butirilcolinesterase , China , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
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