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Planta Med 2009; 75(5): 501-507
DOI: 10.1055/s-0029-1185340
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Biological Evaluation of Structurally Diverse Amaryllidaceae Alkaloids and their Synthetic Derivatives: Discovery of Novel Leads for Anticancer Drug Design

Antonio Evidente1 , Artem S. Kireev2 , Aaron R. Jenkins2 , Anntherese E. Romero2 , Wim F.A. Steelant2 , Severine Van Slambrouck2 , Alexander Kornienko2
  • 1Dipartimento di Scienze, del Suolo, della Pianta, dell'Ambiente e delle Produzioni Animali, Università di Napoli Federico II, Portici, Italy
  • 2Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico, USA
Further Information

Publication History

received October 15, 2008 revised Nov. 4, 2008

accepted Dec. 7, 2008

Publication Date:
23 February 2009 (online)

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Abstract

Twenty-nine Amaryllidaceae alkaloids and their derivatives belonging to the five most common groups, including lycorine, lycorenine, tazettine, crinine, and narciclasine types, were evaluated for antiproliferative, apoptosis–inducing, and anti-invasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine, and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine, and haemanthamine, the apoptosis-inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent anti-invasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The anti-invasive activity of buphanamine is particularly promising because this alkaloid is not toxic to cells even at much higher doses. This work has resulted in the identification of several novel leads for anticancer drug design.

Key words

Amaryllidaceae - alkaloid - apoptosis - invasion - drug lead

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Prof. Dr. Antonio Evidente

Dipartimento di Scienze, del Suolo, della Pianta, dell'Ambiente e delle Produzioni Animali
Università di Napoli Federico II

Via Università 100

80055 Portici

Italy

Phone: + 39 8 12 53 91 78

Fax: + 39 8 12 53 91 86

Email: evidente@unina.it

    www.thieme-connect.de/ejournals/toc/plantamedica