Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives

  • Antonio EvidenteEmail author
  • Alexander Kornienko


Plants of the Amaryllidaceae family have been under intense scrutiny for the presence of the specific metabolites responsible for the medicinal properties associated with them. The study began in 1877 with the isolation of alkaloid lycorine from Narcissus pseudonarcissus and since then more than 100 alkaloids, exhibiting diverse biological activities, have been isolated from the Amaryllidaceae plants. Based on the present scientific evidence, it is likely that isocarbostyril constituents of the Amaryllidaceae, such as narciclasine, pancratistatin and their congeners, are the most important metabolites responsible for the therapeutic benefits of these plant species in the folk medical treatment of cancer. Notably, Narcissus poeticus L., used by the ancient Greek physicians, is now known to contain about 0.12 g of narciclasine per kg of fresh bulbs. The focus of the present research work is the chemistry and biology of these compounds as specifically relevant to their potential use in medicine. In particular, the anticancer evaluation of lycorine, narciclasine as well as of other Amaryllidaceae alkaloids and their synthetic derivatives are presented in this paper. The structure–activity relationships among some groups of Amaryllidaceae alkaloids will be discussed.


Medicinal plants Amaryllidaceae Alkaloids Lycorine Narciclasine Anticancer activity 



This work was carried out within the project “Programma di Scambi Internazionali con Università ed Istituti di Ricerca Stranieri per la Mobilità di Breve Durata di Docenti, Ricercatore e Studiosi”, which is financially supported by the Università di Napoli Federico II anno finanziario 2008. Contribution DISSPAPA 181.


  1. Abou-Donia AH, De Giulio A et al (1991) Narciclasine-4-O-β-D-glcopyranoside, a glucosyloxy amidic phenanthridone derivative from Pancratium maritmum. Phytochemistry 30:3445–3448. doi: 10.1016/0031-9422(91)83226-B CrossRefGoogle Scholar
  2. Abou-Donia AH, Abib AZ et al (1992) Two beatine alkaloids from Egyptian Pancratium maritimum. Phytochemistry 31:2139–2141. doi: 10.1016/0031-9422(92)80381-N CrossRefGoogle Scholar
  3. Arrigoni O, Arrigoni Liso R et al (1975) Lycorine as an inhibitor of ascorbic acid biosynthesis. Nature 256:513–514. doi: 10.1038/256513a0 CrossRefGoogle Scholar
  4. Ceriotti G (1967) Narciclasine: an antimitotic substances from Narcissus bulbs. Nature 213:595–596. doi: 10.1038/213595a0 PubMedCrossRefGoogle Scholar
  5. Cook JW, Loudon JD (1952) The alkaloids. Academic Press, New YorkGoogle Scholar
  6. Evidente A (1991) Narciclasine: 1H- and 13C-NMR data and a new improved method of preparation. Planta Med 57:293–295. doi: 10.1055/s-2006-960098 PubMedCrossRefGoogle Scholar
  7. Evidente A, Motta A (2001) Bioactive metabolites from phytopathogenic bacteria and plants. In: Atta-ur-Rahaman (ed) Studies in natural products chemistry, vol 26. Elsevier, Amsterdam, pp 581–628 (and references therein cited)Google Scholar
  8. Evidente A, Cicala MR et al (1983a) 1H and 13C NMR analysis of lycorine and α-dihydrolycorine. Phytochemistry 22:581–583. doi: 10.1016/0031-9422(83)83051-9 CrossRefGoogle Scholar
  9. Evidente A, Cicala MR et al (1983b) Lycorine structure-activity relationships. Phytochemistry 22:2193–2196. doi: 10.1016/S0031-9422(00)80145-4 CrossRefGoogle Scholar
  10. Evidente A, Iasiello I et al (1983c) Rapid quantitative analysis by reversed-phase high-performance liquid chromatography. J Chromatogr A 281:362–366. doi: 10.1016/S0021-9673(01)87900-0 CrossRefGoogle Scholar
  11. Evidente A, Iasiello I et al (1984) An improved method for large-scale preparation of lycorine. Chem Ind 348–349Google Scholar
  12. Evidente A, Randazzo G et al (1985) Degradation of lycorine by Pseudomonas species strain ITM 311. J Nat Prod 48:564–570. doi: 10.1021/np50040a008 CrossRefGoogle Scholar
  13. Evidente A, Arrigoni O et al (1986) Further experiments on structure-activity relationships among the lycorine alkaloids. Phytochemistry 25:2739–2743. doi: 10.1016/S0031-9422(00)83732-2 CrossRefGoogle Scholar
  14. Evidente A, Abou-Donia AH et al (1999) Nobilisitine A and B, two masanane-type alkaloids from Clivia nobilis. Phytochemistry 51:1151–1155. doi: 10.1016/S0031-9422(98)00714-6 CrossRefGoogle Scholar
  15. Evidente A, Andolfi A et al (2004) (−)-Amarbellisine, a lycorine-type alkaloid from Amayllis belladonna L. growing in Egypt. Phytochemistry 65:2113–2118. doi: 10.1016/j.phytochem.2004.03.020 PubMedCrossRefGoogle Scholar
  16. Evidente A, Andolfi A et al (2005) Minor alkaloids from Clivia nobilis Regel. Alex J Pharm Sci 19:49–53Google Scholar
  17. Evidente A, Kireev AS et al (2009) Biological evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives: discovery of novel leads for anticancer drug design. Planta Med (in press)Google Scholar
  18. Kornienko A, Evidente A (2008) Chemistry, biology, and medicinal potential of narciclasine and its congeners. Chem Rev 108:1982–2014. doi: 10.1021/cr078198u (and references therein cited)PubMedCrossRefGoogle Scholar
  19. Kotera K, Hamada Y et al (1966) Absolute configuration of diastereomeric methiodides in the lycorine-type alkaloids. Tetrahedron Lett 50:6273–6278. doi: 10.1016/S0040-4039(01)84143-5 CrossRefGoogle Scholar
  20. Louw CAM, Regnier TC et al (2002) Medicinal bulbous plants of South Africa and their traditional relevance in the control of infectious disease. J Ethnopharmacol 82:147–154. doi: 10.1016/S0378-8741(02)00184-8 PubMedCrossRefGoogle Scholar
  21. Mondon A, Krohn K (1975) Chemistry of narciclasine. Chem Ber 108:445–463. doi: 10.1002/cber.19751080210 CrossRefGoogle Scholar
  22. Nagakawa Y, Uyeo S et al (1956) The double bond in lycorine. Chem Ind 1238–1239Google Scholar
  23. Piozzi F, Fuganti C et al (1968) Narciclasine and narciprimine. Tetrahedron 24:1119–1131. doi: 10.1016/0040-4020(68)88061-5 CrossRefGoogle Scholar
  24. Piozzi F, Marino M et al (1969) Occurence of non-basic metabolites in Amaryllidaceae. Phytochemistry 8:1745–1748. doi: 10.1016/S0031-9422(00)85963-4 CrossRefGoogle Scholar
  25. Pettit GR, Melody N et al (1994) Antineoplastic agents. 321. Synthesis of 10b-R-hydroxypancratistatin via narciclasine. J Chem Soc Chem Commun 2725–2726. doi: 10.1039/c39940002725
  26. Pettit GR, Melody N et al (2002) Synthesis of 10b(R)-hydroxypancratistatin, 10b(S)-hydroxy-1-epipancratistatin, 10b(S)-hydroxy-1, 2-diepipancratistatin and related isocarbostyrils. Heterocycles 56:139–155CrossRefGoogle Scholar
  27. Wildman WC (1960) The alkaloids. Academic Press, New YorkGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Dipartimento di Scienze, del Suolo, della Pianta, dell’Ambiente e delle Produzioni AnimaliUniversità di Napoli Federico IIPorticiItaly
  2. 2.Department of ChemistryNew Mexico Institute of Mining and Technology SocorroUSA

Personalised recommendations