RESUMO
Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.
Assuntos
Alcaloides de Amaryllidaceae/química , Amaryllidaceae/química , Antineoplásicos Fitogênicos/química , Antiprotozoários/química , Inibidores da Colinesterase/química , Nootrópicos/química , Amaryllidaceae/metabolismo , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Linhagem Celular Tumoral , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Galantamina/química , Galantamina/isolamento & purificação , Galantamina/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Concentração Inibidora 50 , Isoquinolinas/química , Isoquinolinas/isolamento & purificação , Isoquinolinas/farmacologia , Nootrópicos/isolamento & purificação , Nootrópicos/farmacologia , Fenantridinas/química , Fenantridinas/isolamento & purificação , Fenantridinas/farmacologia , Extratos Vegetais/química , Metabolismo SecundárioRESUMO
After ultrasonic-assisted extraction, four lycoris radiata alkaloids: galanthamine, homolycorine, lycorenine, and tazettine were determined by capillary electrophoresis electrochemiluminescence. Polyvinylpyrrolidone was added to the running buffer (RB) to obtain better resolution. Experimental conditions influencing the determination were examined, including the additives, detection potential, separation voltage, injection voltage and time, and RB pH and concentration. Under optimal experimental conditions, the baseline separation of the four alkaloids occurred within 16min. The proposed method displayed the following linear ranges (in ng/mL): galanthamine [60-5000], homolycorine [40-5000], lycorenine [5.0-1500], and tazettine [8.0-2500]. The detection limits in ng/mL, (S/N=3), were galanthamine [14], homolycorine [11], lycorenine [1.8], and tazettine [3.1]. Intra-day and inter-day RSDs for the four alkaloids of the six replicates were less than 2.7% and 3.1%, respectively. The recoveries in% were: tazettine [102.5], lycorenine [98.20], galanthamine [97.30], and homolycorine [98.33].
Assuntos
Alcaloides de Amaryllidaceae/análise , Eletroforese Capilar/métodos , Galantamina/análise , Medições Luminescentes/métodos , Lycoris/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Soluções Tampão , Eletroforese Capilar/economia , Galantamina/isolamento & purificação , Limite de Detecção , Medições Luminescentes/economia , Extratos Vegetais/química , Povidona/química , Sonicação/métodosRESUMO
Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 µM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 µM.
Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Galantamina/isolamento & purificação , Galantamina/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Liliaceae/química , Plantas Medicinais/química , Acetilcolinesterase/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores da Colinesterase/química , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Galantamina/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Concentração Inibidora 50 , Medicina Tradicional , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer's disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.
Assuntos
Alcaloides/química , Inibidores da Colinesterase/química , Galantamina/química , Liliaceae/química , Extratos Vegetais/química , Alcaloides/isolamento & purificação , Argentina , Inibidores da Colinesterase/isolamento & purificação , Cromatografia em Camada Fina , Galantamina/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/químicaRESUMO
Galanthamine, an acetylcholinesterase inhibitor marketed as a hydrobromide salt (Razadyne®, Reminyl®) for the treatment of Alzheimer's disease (AD), is obtained from Amaryllidaceae plants, especially those belonging to the genera Leucojum, Narcissus, Lycoris and Ungernia. The growing demand for galanthamine has prompted searches for new sources of this compound, as well as other bioactive alkaloids for the treatment of AD. In this paper we report the isolation of the new alkaloid 11ß-hydroxygalanthamine, an epimer of the previously isolated alkaloid habranthine, which was identified using NMR techniques. It has been shown that 11ß-hydroxygalanthamine has an important in vitro acetylcholinesterase inhibitory activity. Additionally, Hippeastrum papilio yielded substantial quantities of galanthamine.
Assuntos
Alcaloides , Inibidores da Colinesterase/farmacologia , Colinesterases/metabolismo , Galantamina , Liliaceae/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Cromatografia em Camada Fina , Galantamina/análogos & derivados , Galantamina/isolamento & purificação , Galantamina/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
N-(14-Methylallyl)norgalanthamine, a new natural compound, together with five known alkaloids: N-allylnorgalanthamine, galanthamine, epinorgalanthamine, narwedine, and lycorine were isolated from mother liquors (waste material) obtained after industrial production of galanthamine hydrobromide from Leucojum aestivum leaves. The structures of N-allylnorgalanthamine and N-(14-methylallyl)norgalanthamine were completely determined by (1)H and (13)C NMR spectroscopy and two-dimensional experiments. N-allylnorgalanthamine (IC(50)=0.18microM) and N-(14-methylallyl)norgalanthamine (IC(50)=0.16microM) inhibit AChE considerably more than the approved drug galanthamine (IC(50)=1.82microM).
Assuntos
Alcaloides/química , Inibidores da Colinesterase/química , Galantamina/análogos & derivados , Liliaceae/química , Plantas Medicinais/química , Alcaloides/isolamento & purificação , Alquilação , Inibidores da Colinesterase/isolamento & purificação , Galantamina/isolamento & purificação , Concentração Inibidora 50 , Espectroscopia de Ressonância MagnéticaRESUMO
Using laser confocal microscopical techniques, we observed the anatomical structure of mature root, bulb, and leaf of Lycoris aurea Herb., and also did some research on the localization of galanthamine in the above-mentioned vegetative organ. The results are as follows: In the mature root, the galanthamine distributes mainly in cell wall, especially in cell wall of exodermis and endodermis and vessel wall. In the mature leaf, galanthamine exist in cell wall of vascular bundle, mesophyll cell between vascular bundles and epidermis cells. The scale leaf is the essential accumulational organ. Plenty of galanthamine distribute in the adaxial parenchyma cell, epidermis cell wall, and also in the clingy cell of abaxial epidermis cell.
Assuntos
Proteínas de Arabidopsis/metabolismo , Galantamina/metabolismo , Lycoris/metabolismo , Folhas de Planta/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Sequência de Aminoácidos , Proteínas de Arabidopsis/genética , Sequência de Bases , Galantamina/genética , Galantamina/isolamento & purificação , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Engenharia Genética , Lycoris/citologia , Lycoris/genética , Dados de Sequência Molecular , Nootrópicos/isolamento & purificação , Nootrópicos/metabolismo , Folhas de Planta/química , Folhas de Planta/citologia , Folhas de Planta/genética , Plantas Medicinais/química , Plantas Medicinais/citologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Transformação Bacteriana/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
In recent years, galanthamine isolated from several members of the Amaryllidaceae (Leucojum spp., Narcissus species, Galanthus spp.) has become an important therapeutic options used to slow down the process of neurological degeneration in Alzheimer's disease. This review traces aspects of the history of its development from little known observational studies in the Caucasus Mountains (Southern Russia), to the use of this drug in Eastern European countries (esp. Bulgaria) in the treatment of poliomyelitis and ultimately to the recent introduction onto Western markets in the treatment of Alzheimer's disease. Of note, little is known about the early history of the drug's development and the review also points to other gaps in our knowledge about the ethnopharmacology, pharmacology and clinical use of galanthamine.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Galantamina/uso terapêutico , Galanthus/química , Nootrópicos/uso terapêutico , Doença de Alzheimer/enzimologia , Animais , Disponibilidade Biológica , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacocinética , Ensaios Clínicos como Assunto , Galantamina/isolamento & purificação , Galantamina/farmacocinética , República da Geórgia , Humanos , Nootrópicos/isolamento & purificação , Nootrópicos/farmacocinética , Resultado do TratamentoRESUMO
An analytical assay is presented for the determination of the enantiomeric composition of galanthamine and related synthetic and natural compounds. (-)-Galanthamine is isolated from Galanthus nivalis and is used in this optical pure form in the therapy of Alzheimer's disease. Recent efforts for a total synthesis of unichiral (-)-galanthamine is connected with the need for a fast and reliable assay for the determination of the optical purity of the end product, as well as for optimizing and controlling the final steps in total synthesis particularly the asymmetric transformation of narwedine. In this paper the enantiomeric resolution of these compounds is reported employing a capillary electrophoretic system with beta-cyclodextrin derived chiral selectors. With the proposed system a number of galanthamine and narwedine derived analogous compounds could be separated, including 1-bromo- and N-alkyl-substituted compounds.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Eletroforese Capilar/métodos , Galantamina/isolamento & purificação , Nootrópicos/isolamento & purificação , Galantamina/química , Galantamina/uso terapêutico , Galanthus , Humanos , Nootrópicos/química , Nootrópicos/uso terapêutico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , EstereoisomerismoRESUMO
Galanthamine, an alkaloid present in the Amaryllidaceae is currently undergoing clinical trials for the treatment of Alzheimer's. Common daffodils, Narcissus spp., contain galanthamine and other alkaloids. Four commercial Narcissus cultivars were evaluated as potential sources of galanthamine. Planting depths, planting densities, bulb size or flower bud removal did not affect galanthamine content.