Research on the Alkaloids of Amaryllidaceae Plants: Genera Lycoris and Hippeastrum

dc.contributor
Universitat de Barcelona. Departament de Productes Naturals, Biologia Vegetal i Edafologia
dc.contributor.author
Guo, Ying
dc.date.accessioned
2015-11-13T08:05:14Z
dc.date.available
2015-11-13T08:05:14Z
dc.date.issued
2015-11-05
dc.identifier.uri
http://hdl.handle.net/10803/318797
dc.description.abstract
The Amaryllidaceae alkaloids represent a large and still expanding group of isoquinoline alkaloids, usually classified into nine skeleton types whose representative compounds are: norbelladine, lycorine, homolycorine, crinine, haemanthamine, narciclasine, tazettine, montanine and galanthamine. To date, the alkaloids have been isolated from plants of this family, showing a broad range of biological effects, including acetylcholinesterase (AChE)-inhibitory, antitumor, antibacterial, antifungal, antiviral and antimalarial activities. The genus Lycoris, a group of Amaryllidaceae plants distributed in temperate regions of Eastern Asia, is already known for containing representative alkaloids typical of this botanical family with a wide range of biological activities (for example, lycorine and galanthamine). In the work, the alkaloid profiles of nine species, L. albiflora, L. aurea, L. chinensis, L. haywardii, L. incarnata, L. longituba, L. radiata, L. sprengeri, and L. squamigera, and one variety (L. radiata var. pumila) have been evaluated by GC-MS. This study has identified a total of 31 alkaloids. Structures belonging to the lycorine-, homolycorine-, haemanthamine-, narciclasine-, tazettine-, montanine- and galanthamine-series were identified and quantified, with galanthamine- and lycorine-type alkaloids predominating and usually showing a high relative abundance in comparison with other alkaloids of the extracts. All detected and identified alkaloids had been characterized previously. The analysis of bioactive Amaryllidaceae alkaloid profiles in 9 species and one variety of Lycoris by GC-MS revealed some similarities and differences. This kind of analysis could be useful in guiding the search for compounds with pharmacological activity. Among the species analyzed in the work, L. longituba revealed itself to be a potential commercial source of bioactive alkaloids (such as galanthamine and lycorine) due to its high content in comparison with the other species. In general terms, our results are consistent with the alkaloid profiles reported in the literature for previously studied species. Finally, the GC-MS technology applied has demonstrated to be sufficiently sensitive for the detection of Amaryllidaceae alkaloids, allowing the application of quantitative methodologies to obtain valuable information in relatively short times. The Hippeastrum is a well-known ornamental Amaryllidaceae genus from South America and South Africa, particularly Brazil. Three novel Amaryllidaceae alkaloids form the species Hippeastrum papilio were isolated, including hippapiline, papiline and 3-O-(3’-hydroxybutanoyl)haemanthamine. Their structures were determined by physical and spectroscopic methods. In addition, the known alkaloids haemanthamine, galanthamine, narwedine, 11β-hydroxygalanthamine, apogalanthamine and 9-O-demethyllycosinine B were identified. The unusual cis-B/C ring fusion for the new homolycorine representative hippapiline was ratified by NMR and CD spectroscopy. Besides, GC-MS analysis revealed that galanthamine was the main constituent in the n-hexane extract (86.3 %), also featuring as one of the major components in the EtOAc extract (39.0 %). A crinine-type alkaloid, 3-O-methyl-epimacowine was identificated in the indigenous Brazilian species Hippeastrum calyptratum. Furthermore, the ongoing search for alkaloids in the Amaryllidaceae species using GC-MS resulted in the identification of 18 alkaloids. In addition, the absolute stereochemistry of the 5,10b-ethano bridge in the crinine variants was determined by circular dichroism and X-ray crystallographic analysis, affording the first direct evidence for the presence of crinine-type alkaloids in the genus Hippeastrum. Parasitic protozoa in vitro assays were performed on the new alkaloids from H. papilio. The alkaloid papiline showed favorable activity against Trypanosoma brucei rhodesiense (STIB 900 strain, trypomastigotes stadium) with an IC50 of 0.523 mg/ml, and low activity against Leishmania donovani. Additionally, 3-O-(3’-hydroxybutanoyl)haemanthamine showed mild activity against T. cruzi, low activity against L. donovani and Plasmodium falciparum and also showed low cytotoxicity against myoblasts (L-6 cells). Overall, the research has once again demonstrated the enormous potential of the Amaryllidaceae (subfamily Amaryllidoideae) plants as sources of bioactive products and novel alkaloids, and confirmed the importance of continuing research on species not yet explored.
eng
dc.description.abstract
La familia Amaryllidaceae presenta un grupo específico de alcaloides isoquinolínicos, que suelen mostrar un amplio espectro de actividades biológicas. Se han seleccionado para su estudio 9 especies del género Lycoris (L. albiflora, L. aurea, L. chinensis, L. haywardii, L. incarnata, L. longituba, L. radiata, L. sprengeri, and L. squamigera) y una variedad L. radiata var. pumila. El género Lycoris presenta numerosos endemismos en China. Las especies Hippeastrum papilio y H. calyptratum originarias de Brasil también han sido objeto de estudio. Por lo que respecta a las especies estudiadas del género Lycoris, la identificación de sus alcaloides se ha llevado a cabo por GC-MS. Este estudio ha permitido identificar un total de 31 alcaloides. En el perfil de los extractos de las especies estudiadas predominan los alcaloides que presentan un acoplamiento fenol-oxidativo orto-para’ (tipo licorina) y para-orto’ (tipo galantamina). El número de alcaloides detectado en cada una de las especies estudiadas oscila entre 10 (L. incarnata y L. radiata var. pumila) y 20 (L. longituba) compuestos. Todos los alcaloides detectados e identificados habían sido caracterizados con anterioridad. En el estudio de Hippeastrum papilio se constató la presencia del alcaloide galantamina en cantidades notables –de interés por su utilización como tratamiento paliativo de la Enfermedad de Alzheimer-, además de los nuevos compuestos hippapilina, papilina y 3-O-(3’-hidroxibutanoil)hemantamina junto a los ya conocidos 11β-hidroxigalantamina, apogalantamina, hemantamina, narwedina y 9-O-demethyllycosinine B. El alcaloide hippapilina es el primer ejemplo de fusión cis B/C con los protones 10b y 1 en orientación beta. Por su parte, el alcaloide papilina muestra una remarcable actividad frente a Trypanosoma brucei rhodesiense (cepa STIB 900, estadio tripomastigote) con un IC50 de 0.523 μg/ml. Finalmente, el estudio de la especie Hippeastrum calyptratum nos ha permitido la identificación de 17 compuestos, de los cuales el alcaloide del tipo crinina 3-O-metilepimacowina, se aisla por primera vez de una fuente natural.
spa
dc.format.extent
196 p.
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Universitat de Barcelona
dc.rights.license
ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.
dc.source
TDX (Tesis Doctorals en Xarxa)
dc.subject
Alcaloides
dc.subject
Alkaloids
dc.subject
Amaril·lidàcies
dc.subject
Amarilidáceas
dc.subject
Amaryllidaceae
dc.subject
Ressonància magnètica nuclear
dc.subject
Resonancia magnètica nuclear (Física)
dc.subject
Nuclear magnetic resonance
dc.subject
Cromatografia de gasos
dc.subject
Cromatografía de gases
dc.subject
Gas chromatography
dc.subject
Espectrometria de masses
dc.subject
Espectrometría de masas
dc.subject
Mass spectrometry
dc.subject.other
Ciències de la Salut
dc.title
Research on the Alkaloids of Amaryllidaceae Plants: Genera Lycoris and Hippeastrum
dc.type
info:eu-repo/semantics/doctoralThesis
dc.type
info:eu-repo/semantics/publishedVersion
dc.subject.udc
58
cat
dc.contributor.director
Bastida Armengol, Jaume
dc.contributor.director
Viladomat Meya, Francesc
dc.contributor.tutor
Bastida Armengol, Jaume
dc.embargo.terms
cap
dc.rights.accessLevel
info:eu-repo/semantics/openAccess
dc.identifier.dl
B 27953-2015


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