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

• Autores: Ying Guo
• Directores de la Tesis: Francisco Viladomat Meya (dir. tes.), Jaume Bastida i Armengol (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Antonio Fernández Tiburcido (presid.), Strahil Berkov (secret.), José Luis Ríos Cañavate (voc.)
• Materias:
  • Química
    • Química analítica
      • Espectroscopia de resonancia magnética
    • Bioquímica
      • Alcaloides
• Enlaces
  • Tesis en acceso abierto en:  TDX  Dipòsit Digital de la UB 
• Resumen

  • 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, 11?-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 identi?cation 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.