Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 250
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Alkaloids Chem Biol ; 83: 113-185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32098649

RESUMO

The Amaryllidaceae alkaloids are a distinctive chemotaxonomic feature of the subfamily Amaryllidoideae of the family Amaryllidaceae, which consists of 59 genera and >800 species distributed primarily in tropical and subtropical areas. Since the first isolation, ca. 140 ago, >600 structurally diverse Amaryllidaceae alkaloids have been reported from ca. 350 species (44% of all species in the subfamily). A few have been found in other plant families, but the majority are unique to the Amaryllidoideae. These alkaloids have attracted considerable research interest due to their wide range of biological and pharmacological activities, which have been extensively reviewed. In this chapter we provide a review of the 636 structures of isolated or tentatively identified alkaloids from plants of the Amaryllidoideae and their classification into 42 skeleton types, as well as a discussion on their distribution, and chemotaxonomical and chemoecological aspects.


Assuntos
Alcaloides de Amaryllidaceae/química , Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/metabolismo , Estrutura Molecular
2.
Nat Prod Res ; 34(2): 233-240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30636443

RESUMO

A new narciclasine glycoside, narciclasine-4-O-ß-D-xylopyranoside (1) was characterised along with four known alkaloids pancratistatin (2), 1-O-(3-hydroxybutyryl) pancratistatin (3), vittatine (4), 9-O-demethylgalanthine (5) from Zephyranthes minuta. Their structures were established on the basis of spectroscopic data analysis. The in vitro cytotoxic study of extract, fractions and isolated compounds against two human cancer cell lines (KB and SiHa) indicated the potential activity of extract and n-butanol fraction due to presence of active alkaloids pancratistatin, 1-O-(3-hydroxybutyryl) pancratistatin, lycorine and haemanthamine.


Assuntos
Alcaloides de Amaryllidaceae/isolamento & purificação , Amaryllidaceae/química , Glicosídeos/isolamento & purificação , Fenantridinas/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Glicosídeos Cardíacos , Linhagem Celular Tumoral , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Glicosídeos/química , Humanos , Isoquinolinas/farmacologia , Fenantridinas/química , Fenantridinas/farmacologia , Extratos Vegetais/química
3.
J Ethnopharmacol ; 248: 112305, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31639490

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The development of selective inhibitors of monoamine oxidase B (MAO-B) has been essential in treating Parkinson's disease. However, the apparent hepatotoxicity and drug-drug interactions of current inhibitors accentuate the need for the development of novel pharmacotherapies. Crossyne guttata (L.) D. & U. Müll-Doblies is used frequently by Rastafarian bush doctors to treat alcoholism, a disorder which is also accentuated by MAO. OBJECTIVE: The study sought to isolate, identify and characterise the biologically active constituents of C. guttata based on their ability to inhibit the MAO enzymes. MATERIALS AND METHODS: Column chromatography was used to isolate the biologically active alkaloids of C. guttata. The ability of the alkaloids to inhibit the biotransformation of 4-aminoantipyrine by the MAO enzymes was evaluated in vitro. In silico docking was conducted using AutoDock Vina server while the pharmacokinetic properties of the compounds were evaluated using SwissADME. RESULTS: Chromatographic separation of an ethanolic fraction of C. guttata yielded the alkaloids crinamine 1 and epibuphanisine 2. 1 and 2 along with structurally related alkaloids haemanthamine 3 and haemanthidine 4 were evaluated for their ability to inhibit the action of isozymes of MAO in vitro. Alkaloids effected submicromolar IC50 values against MAO-B, the most potent of which being crinamine 1 (0.014 µM) > haemanthidine 4 (0.017 µM) > epibuphanisine 2 (0.039 µM) > haemanthamine 3 (0.112 µM). Binding energies of the alkaloids correlated well with their inhibitory potential with crinamine displaying the best binding efficacy and binding energy score with MAO-B. DISCUSSION AND CONCLUSION: Crinamine and epibuphanisine exhibited potent and selective inhibitory activity towards MAO-B. After comprehensive in silico investigations encompassing robust molecular docking analysis, the drug-like attributes and safety of the alkaloids suggest the crinamine is a potentially safe drug for human application.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Modelos Biológicos , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacocinética , Alcaloides de Amaryllidaceae/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Humanos , Monoaminoxidase/química , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacocinética , Inibidores da Monoaminoxidase/toxicidade , Mutação , Segurança do Paciente , Conformação Proteica , Medição de Risco , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Relação Estrutura-Atividade , Células Vero
4.
J Pharm Biomed Anal ; 176: 112811, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31437748

RESUMO

A simple and valid method for rapid screening of cathepsin B inhibitors from traditional Chinese medicines (TCMs) was established by the combination of immobilized enzyme microreactor (IMER) and capillary electrophoresis. Cathepsin B was immobilized on the inner surface of the capillary by glutaraldehyde method. The separation of substrate and product could be finished by baseline within 3 min. The activity of the immobilized cathepsin B remained approximately 90% after 50 runs. The quantification and statistical analysis of the product peak area was used to evaluate the catalytic activity of cathepsin B. The value of Michaelis-Menten constant of cathepsin B was 0.85 mM. The half-maximal inhibitory concentration (IC50) of L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) was measured as 36.08 nM, which indicated that the cathepsin B reactor was successfully developed and was feasible for inhibitorscreening. The raised method was then applied to discover the inhibitory potential of 17 standard compounds from traditional Chinese medicines. Five natural products, including kaempferol, rutaecarpine, evodiamine, theophylline, lycobetaine showed potential inhibition for cathepsin B. Additionally, molecular docking study was investigated for supporting the interaction between enzyme and inhibitors.


Assuntos
Catepsina B/antagonistas & inibidores , Descoberta de Drogas/métodos , Medicamentos de Ervas Chinesas/análise , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/farmacologia , Catepsina B/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Eletroforese Capilar/métodos , Enzimas Imobilizadas/química , Estudos de Viabilidade , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Indolizinas/química , Indolizinas/isolamento & purificação , Indolizinas/farmacologia , Quempferóis/química , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Simulação de Acoplamento Molecular , Quinazolinas/química , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologia , Teofilina/química , Teofilina/isolamento & purificação , Teofilina/farmacologia
5.
Biomed Res Int ; 2019: 1851740, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275963

RESUMO

The human opportunistic fungal pathogen Candida albicans causes a severe health burden while the biofilms formed by C. albicans present a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs against C. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) against C. albicans. The minimal inhibitory concentration (MIC) of LH against C. albicans SC5314 was 64 µM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC50) above 256 µM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fight C. albicans infections.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Candida albicans/patogenicidade , Fenantridinas/farmacologia , Adesividade/efeitos dos fármacos , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/toxicidade , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Morte Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hifas/efeitos dos fármacos , Fenantridinas/química , Fenantridinas/toxicidade , Fosfolipases/metabolismo , Virulência/efeitos dos fármacos
6.
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
7.
J Pharm Biomed Anal ; 175: 112750, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330284

RESUMO

Narcissus tazetta is used traditionally for treatment of sores, wounds, skin diseases, cancer in different parts of world. Present study focus on the analysis of amaryllidaceae alkaloids in this plant using an ultra-performance liquid chromatography-diode array detection method. The method was developed for simultaneous quantification of eight Amaryllidaceae alkaloids i.e. pseudolycorine (1), lycorine (2), galanthamine (3), 8-O-demethylhomolycorine (4), N-methylhaemanthidine chloride (5), homolycorine (6), narciclasine (7) and zefbetaine (8) in Narcissus tazetta. The method was validated using a BEH C18 column with linear gradient. Standard calibration curve for the analytes showed good linearity ( r2≥0.999). The method was validated for intra-day (RSDs<0.91%) and inter-day (RSDs<0.65%) precisions and accuracy (recovery 92.2-112.5%). The developed method was successively applied for studying the variation of alkaloids in different parts of Narcissus tazetta, i.e. bulbs, roots, flowers, flower stalks and leaves. The study showed a significant variation of these alkaloids in different parts of the plant. Among the alkaloids under investigation, pseudolycorine had highest content in all the parts. Furthermore, application of the developed method to the identification of phytocomponents allowed the identification of sixteen alkaloids.


Assuntos
Alcaloides de Amaryllidaceae/química , Narcissus/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Flores/química , Galantamina/química , Fenantridinas/química , Folhas de Planta/química , Raízes de Plantas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
8.
J Pharm Biomed Anal ; 172: 230-237, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060036

RESUMO

Narcissus spp. are an economically important crop for medicines in relation with the alkaloids production, mainly galanthamine, an acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease. In this article an extensively study of the phytochemistry of both bulbs of different species and varieties of Narcissus grown in Iran and in vitro culture of these plants was investigated. In particular, the Amaryllidaceae alkaloid profile and the galanthamine and lycorine contents in wild bulbs of Narcissus papyraceus (G5) and four varieties of Narcissus tazetta (N. tazetta var. Shahla (G4), N. tazetta var. Shastpar (G1), N. tazetta var. Meskin (G2), N. tazetta var. Panjehgorbei (G3)), growing in Iran are reported. The alkaloid profiles were investigated by GC-MS and LC-MS and the quantitative analysis was performed using GC-MS. In total, thirty alkaloids were identified among them nine alkaloids were observed with the both methods of analysis. The variety Meskin of N. tazetta (G2), showed the highest diversity of alkaloids and the highest content in galanthamine. On this last species (G2) and on N. tazetta var. Shahla (G4), the effects of auxins 2,4-dichlorophenoxyacetic acid (2,4-D), 4-amino-3,5,6-trichloropicolinic acid (Picloram) and naphthalene acetic acid (NAA) at concentrations of 25 and 50 µM were studied on the induction of callus and its capacity to induce organogenesis and alkaloid diversity. All auxins, at the concentrations of 25 and 50 µM, produced calli. Bulblets and roots were formed on calli grown only in the presence of 25 or 50 µM NAA. GC-MS analyses showed the presence of galanthamine and lycorine in calli, roots and bulblets, with all auxins whatever the concentration used while demethylmaritidine and tazettine were found in differentiated tissue cultures cultivated on the medium containing NAA (25 or 50 µM) or in calli initiated with Picloram (50 µM). Precursor 4'-O-methylnorbelladine (MN) of Amaryllidaceae alkaloids feeding was found to significantly improve the accumulation of both galanthamine (82 µg/g DW) and lycorine (1800 µg/g DW) in bulblets of N. tazetta var. Meskin (G2).


Assuntos
Alcaloides de Amaryllidaceae/química , Narcissus/química , Inibidores da Colinesterase/química , Galantamina/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Irã (Geográfico) , Fenantridinas/química , Extratos Vegetais/química , Raízes de Plantas/química
9.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987121

RESUMO

Twelve derivatives 1a-1m of the ß-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3ß (GSK-3ß) inhibition potency was evaluated in the active derivatives. In order to reveal the availability of the drugs to the CNS, we elucidated the potential of selected derivatives to penetrate through the blood-brain barrier (BBB). Two compounds, namely 11-O-(2-methylbenzoyl)-haemanthamine (1j) and 11-O-(4-nitrobenzoyl)-haemanthamine (1m), revealed the most intriguing profile, both being acetylcholinesterase (hAChE) inhibitors on a micromolar scale, with GSK-3ß inhibition properties, and predicted permeation through the BBB. In vitro data were further corroborated by detailed inspection of the compounds' plausible binding modes in the active sites of hAChE and hBuChE, which led us to provide the structural determinants responsible for the activity towards these enzymes.


Assuntos
Doença de Alzheimer/metabolismo , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/metabolismo , Amaryllidaceae/química , Amaryllidaceae/metabolismo , Fenantridinas/química , Fenantridinas/metabolismo , Barreira Hematoencefálica/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Molecular , Permeabilidade , Relação Estrutura-Atividade
10.
Phytomedicine ; 60: 152832, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31031043

RESUMO

BACKGROUND: Successful cancer chemotherapy is hampered by resistance of cancer cells to established anticancer drugs. Numerous natural products reveal cytotoxicity towards tumor cells. PURPOSE: The present study was aimed to determine the cytotoxicity of a betaine-type alkaloid, ungeremine, towards 9 cancer cell lines including various sensitive and drug-resistant phenotypes. The mode of action of this compound was further investigated. METHODS: The cytotoxicity, ferroptotic and necroptotic cell death were determined by the resazurin reduction assay. Caspase activation was evaluated using the caspase-Glo assay. Flow cytometry was applied for the analysis of cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). Apoptotic, necroptotic and autophagic markers were determined by Western blotting. CCRF-CEM leukemia cells were used for all mechanistic studies. RESULTS: Ungeremine displayed cytotoxic activity towards the 9 cancer cell lines tested, including drug-sensitive and MDR phenotypes. The IC50values obtained varied from 3.67 µM (in MDA-MB-231-BCRP breast carcinoma cells) to 75.24 µM (against in CEM/ADR5000 leukemia cells) for ungeremine and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin (control drug). Ungeremine induced ferroptosis, necroptosis, autophagy as well as apoptosis mediated by caspase activation, MMP alteration and increase ROS production. CONCLUSION: The present investigation showed that ungeremine is a promising cytotoxic compoundthat could be further explored in the future to develop new anticancer drugs to fight sensitive and resistant phenotypes.


Assuntos
Alcaloides/toxicidade , Alcaloides de Amaryllidaceae/toxicidade , Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Indolizinas/toxicidade , Extratos Vegetais/toxicidade , Alcaloides de Amaryllidaceae/química , Antineoplásicos Fitogênicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Indolizinas/química , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo
11.
Eur J Med Chem ; 173: 76-89, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30986573

RESUMO

A series of (±)-trans-dihydronarciclasine and (±)-trans-dihydrolycoricidine derivatives with variously substituted ring A was synthesised and evaluated for their antiproliferative activity against 60 human tumour cell lines (NCI60), representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, as well as kidney in vitro. Among the 13 alkaloids screened, (±)-trans-dihydronarciclasine showed the highest potency as a cytotoxic molecule. A structure-activity relationship (SAR) study indicated that the presence of a hydroxy group at position 7 and a rigid, 1,3-benzodioxole scaffold were essential for the antiproliferative activity.


Assuntos
Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/farmacologia , Antineoplásicos/farmacologia , Alcaloides/síntese química , Alcaloides/química , Alcaloides de Amaryllidaceae/síntese química , Alcaloides de Amaryllidaceae/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
12.
Planta Med ; 85(8): 637-647, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30909312

RESUMO

The spread of malaria is thought to have followed human expansion out of Africa some 60 - 80 thousand years ago. With its prevalence in pantropical countries of the world and epicenter localized in Africa, malaria is now considered an unnecessary burden to overworked and under-resourced healthcare structures. Plants have long afforded a fertile hunting ground for the search and identification of structurally diverse antimalarial agents, such as quinine and artemisinin. This survey examines the antiparasitic properties of the family Amaryllidaceae via the antiplasmodial activities demonstrated for its lycorane alkaloid principles. Of these, 24 were natural compounds identified in 20 species from 11 genera of the Amaryllidaceae family, whilst the remaining 28 were synthetically derived entities based on the lycorane skeleton. These were screened against ten different strains of the malarial parasite Plasmodium falciparum, wherein the parent compound lycorine was shown to be the most potent with an IC50 of 0.029 µg/mL in the FCR-3 strain seen to be the best. Structure-activity relationship studies revealed that good activities were detectable across both the natural compounds as well as the synthetically accessed derivatives. Such studies also highlighted that there are several inherent structural features that define the lycorane alkaloid antiplasmodial pharmacophore, such as the nature of its ring systems and properties of its substituents. Mechanistically, a limited number of studies confirmed that lycorane alkaloids manifest their action by targeting enzymes associated with the plasmodial FAS-II biosynthetic pathways. Overall, these alkaloids have provided useful, convenient, and accessible scaffolds for antimalarial-based drug discovery.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Antimaláricos/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Humanos , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
13.
Chem Biodivers ; 16(5): e1800662, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30801949

RESUMO

Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine-type compound (6-hydroxymaritidine) was tested as an inhibitor against acetyl- and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure-activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.


Assuntos
Alcaloides/química , Alcaloides de Amaryllidaceae/química , Amaryllidaceae/química , Inibidores da Colinesterase/química , Fenantridinas/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Alcaloides/metabolismo , Alcaloides/farmacologia , Amaryllidaceae/metabolismo , Sítios de Ligação , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Domínio Catalítico , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Relação Estrutura-Atividade
14.
J Sep Sci ; 42(3): 684-690, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30488652

RESUMO

The separation of minor compounds, especially those with similar polarities from a complex sample, remains challenging. In the proposed study, an effective method based on medium-pressure liquid chromatography and recycling high-speed counter-current chromatography was developed for the enrichment and separation of three minor components from Dracocephalum tanguticum. The crude extract was directly introduced to medium-pressure liquid chromatography for the enrichment of the three minor components. Based on high-performance liquid chromatography analysis, the total content of these three compounds increased from 0.48% in the crude extract to 85.3% in the medium-pressure liquid chromatography fraction. In addition, high-speed counter-current chromatography was employed to separate the enriched compounds using the solvent system hexane/ethyl acetate/methanol/water (1.18:8.82:1.18:8.82, v/v/v/v). As a result, compound 3 and a mixture of compounds 1 and 2 were obtained. In order to improve the resolution of compounds 1 and 2 while saving separation time, a recycling and heart-cut mode was used. Finally, compounds 1 and 2 were obtained after five cycles. These compounds were identified as 3-phenylethyl ß-d-glucopyranoside (1), tazettoside E (2), and cirsiliol-4'-glucoside (3). Compounds 1 and 2 were primarily separated from D. tanguticum. Moreover, the developed method provided a reference for the separation of minor components from the complex sample.


Assuntos
Alcaloides de Amaryllidaceae/isolamento & purificação , Distribuição Contracorrente , Glucose/isolamento & purificação , Lamiaceae/química , Componentes Aéreos da Planta/química , Pressão , Alcaloides de Amaryllidaceae/química , Cromatografia Líquida de Alta Pressão , Glucose/análogos & derivados , Glucose/química
15.
Phytochem Anal ; 30(3): 268-277, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30548356

RESUMO

INTRODUCTION: Lycorine, one of the most common alkaloids in Lycoris spp., is believed to possess pharmacological activity. OBJECTIVE: To discover and identify lycorine-type alkaloids in the crude extracts of bulbs from six Lycoris spp. by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) detection. METHODOLOGY: A qualitative analytical method with a data mining strategy was utilised. Based on the fragmentation patterns of standards investigated in positive tandem mass spectrometry (MS/MS) mode, the fragmentation rules of lycorine-type alkaloids were summarised. These types of alkaloids were additionally classified as different subtypes based on structural features and MS/MS fragmentation patterns, and the diagnostic ions for characterisation of different subtypes of alkaloids were designated. RESULTS: Thirty-seven lycorine type alkaloids, including 16 previously undescribed compounds, were efficiently screened out and tentatively identified from the crude extracts of six Lycoris spp. Lycoris sprengri may be a preferable species for studying or extracting lycorine-type alkaloids because of elevated relative concentrations and highest diversity of alkaloids. CONCLUSION: The UHPLC-QTOF-MS and MS/MS data-mining strategy proved useful for the detection and tentative identification of lycorine-type alkaloids in bulbs of Lycoris spp. and could be extended to other Amaryllidaceae genera. The consequent profiling of the lycorine-type alkaloids will be useful in the quality control of raw materials of Lycoris species and the exploration of superior species.


Assuntos
Alcaloides de Amaryllidaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Lycoris/química , Fenantridinas/química , Espectrometria de Massas em Tandem/métodos , Mineração de Dados , Lycoris/classificação , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Especificidade da Espécie , Estereoisomerismo
16.
Org Lett ; 20(18): 5894-5898, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30204451

RESUMO

The synthesis of a 52-member compound collection from the natural product lycorine is reported, highlighted by divergent cross-coupling and substitution strategies and an unusual ring rearrangement induced by reaction with aryne intermediates.


Assuntos
Alcaloides de Amaryllidaceae/síntese química , Produtos Biológicos/síntese química , Fenantridinas/síntese química , Alcaloides de Amaryllidaceae/química , Produtos Biológicos/química , Estrutura Molecular , Fenantridinas/química , Estereoisomerismo
17.
Biomed Pharmacother ; 107: 615-624, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30114645

RESUMO

Nature is the most abundant source for novel drug discovery. Lycorine is a natural alkaloid with immense therapeutic potential. Lycorine is active in a very low concentration and with high specificity against a number of cancers both in vivo and in vitro and against various drug-resistant cancer cells. This review summarized the therapeutic effect and the anticancer mechanisms of lycorine. At the same time, we have discussed the pharmacology and comparative structure-activity relationship for the anticancer activity of this compound. The researches outlined in this paper serve as a foundation to explain lycorine as an important lead compound for new generation anticancer drug design and provide the principle for the development of biological strategies to utilize lycorine in the treatment of cancers.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Fenantridinas/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacocinética , Humanos , Modelos Biológicos , Fenantridinas/química , Fenantridinas/farmacocinética , Relação Estrutura-Atividade
18.
J Org Chem ; 83(17): 9968-9977, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30005155

RESUMO

Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (-)-crinine, (-)-crinane, (-)-amabiline, (+)-mesembrine, (-)-maritidine, (-)-oxomaritidine, and (+)-mesembrane is reported. Scaffold 1 is found as a prime structural motif in a wide variety of the AAs and is a novel synthon toward designing a divergent route for the synthesis of these natural products. This is established in a few steps, starting from a chiral aza-bicyclo-heptene sulfone scaffold (2) via conjugate addition and concomitant stereoselective ring opening with allylmagnesium bromide, a key step that generates a crucial quaternary stereocenter, fixing the stereochemistry of the rest of the molecule at an early stage. One carbon truncation followed by intramolecular reductive amination led to the desired core 1 in a multigram scale.


Assuntos
Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/síntese química , Técnicas de Química Sintética , Indóis/química , Modelos Moleculares , Conformação Molecular , Fenantridinas/química , Estereoisomerismo
19.
Fitoterapia ; 129: 78-84, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29928968

RESUMO

Jonquailine, a new alkaloid recently isolated from Narcissus jonquilla quail, an Amaryllidaceae species cultivated for its flowers fragrance in Europe and USA, shows very significant anti-proliferative activity against several malignant cancer cell types. Although it was reported that this activity is related to the functionalities and to its stereochemistry at C-8 of B ring, the absolute configuration at this stereocenter was not known. Density functional theory (DFT) calculations of chiroptical properties, namely electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD) are employed here to complete assignment of absolute configuration of jonquailine, and then, by extension, to its analogues pretazettine and 8-O-methylpretazettine. While ECD is not discriminating and ORD is of limited use, VCD reveals decisive in the task of absolute configuration assignment.


Assuntos
Alcaloides de Amaryllidaceae/química , Amaryllidaceae/química , Dicroísmo Circular , Estrutura Molecular , Dispersão Óptica Rotatória , Raízes de Plantas/química
20.
Zhongguo Zhong Yao Za Zhi ; 43(10): 2086-2090, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-29933675

RESUMO

Three aporphine-type alkaloids (1-3), three lycorine-type alkaloids (4-6), two crinane type alkaloids (7, 8) and one phenanthridine-type alkaloid (9) were isolated from the chloroform soluble fraction of 70% ethanol extract of the bulbs of Lycoris radiata through various column chromatographies over silica gel, ODS, Sephadex LH-20 and MCI. Their structures were elucidated as (+)-N-methoxylcarbonyl-1,2-methylenedioxyl-isocorydione (1), isocorydione (2), 8-demethyl-dehydrocrebanine (3), (+)-3-hydroxy-anhydrolycorine N-oxide (4), vasconine (5), pancratinine D (6), yemenine A (7), 11-O-acetylhaemanthamine (8), and 5,6-dihydro-5-methyl-2-hydroxyphenanthridine (9) based on their chemical and physicochemical properlies and spectroscopic data. Compound 1 was a new compound and alkaloids 2-9 were isolated and identified from this plant for the first time.


Assuntos
Alcaloides de Amaryllidaceae/isolamento & purificação , Lycoris/química , Alcaloides de Amaryllidaceae/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Raízes de Plantas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA