Alkaloids from Leucojum vernum and Antiretroviral Activity of Amaryllidaceae Alkaloids

László Szlávik; Ágnes Gyuris; János Minárovits; Peter Forgo; József Molnár; Judit Hohmann

doi:10.1055/s-2004-827239

Planta Medica, Table of Contents

Planta Med 2004; 70(9): 871-873
DOI: 10.1055/s-2004-827239

Letter

Alkaloids from Leucojum vernum and Antiretroviral Activity of Amaryllidaceae Alkaloids

László Szlávik¹ , Ágnes Gyuris¹ , János Minárovits¹ , Peter Forgo² , József Molnár³ , Judit Hohmann⁴

¹Johan Béla National Centre for Epidemiology, Microbiological Research Group, Budapest, Hungary
²Department of Organic Chemistry, University of Szeged, Szeged, Hungary
³Department of Medical Microbiology, University of Szeged, Szeged, Hungary
⁴Department of Pharmacognosy, University of Szeged, Szeged, Hungary

Abstract

Three alkaloids, lycorine, homolycorine and 2-O-acetyllycorine, were isolated from the bulbs of Leucojum vernum (Amaryllidaceae) and identified by means of NMR analysis. The alkaloids obtained from L. vernum and from other Amaryllidaceae species were studied in vitro for HIV-1 replication inhibitory activity on MT4 cells. The cytotoxicity of the compounds in uninfected cells was evaluated by using the MTT assay and the [³ H]thymidine incorporation test. The antiviral activities were determined by means of the p24 antigen assay and solid-phase reverse transcriptase testing. The results demonstrate that trisphaeridine, lycorine, homolycorine, and haemanthamine possess high antiretroviral activities (IC₅₀ = 0.4 - 7.3 μg/mL), accompanied by low therapeutic indices (TI₅₀ = 1.3 - 1.9).

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References

1 Gabrielsen B, Monath T P, Huggins J W, Kefauver D F. Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances. J Nat Prod. 1992; 55 1569-81
2 Ieven M, Van den Berghe D A, Vlietinck A J. Plant antiviral agents IV. Influence of lycorine on growth pattern of three animal viruses. Planta Medica. 1983; 49 109-14
3 Ieven M, Vlietinck A J, Van den Berghe D A, Totte J. Plant antiviral agents III. Isolation of alkaloids from Clivia miniata Regel (Amaryllidaceae). J Nat Prod. 1982; 45 564-73
4 Zee-Cheng R K, Yan S J, Cheng C C. Antileukemic activity of ungeremine and related compounds. Preparation of analogues of ungeremine by a practical photochemical reaction. J Med Chem. 1978; 21 199-203
5 Karadeniz H, Gulmez B, Sahinci F, Erdem A, Kaya G I, Unver N. et al . Disposable electrochemical biosensor for the detection of the interaction between DNA and lycorine based on guanine and adenine signals. J Pharmaceut Biomed Anal. 2003; 33 295-302
6 Schmeda-Hirschmann G, Astudillo L, Bastida J, Viladomat F, Codina C. DNA binding activity of Amaryllidaceae alkaloids. Bol Soc Chil Quim. 2000; 45 515-8
7 Hohmann J, Forgo P, Molnár J, Wolfard K, Molnár A, Thalhammer T, Máthé I, Sharples D. Antiproliferative Amaryllidaceae alkaloids isolated from the bulbs of Sprekelia formosissima and Hymenocallis x festalis . Planta Medica. 2002; 68 454-7
8 Jeffs P W, Abou-Donia A, Campau D, Staiger D. Structures of 9-O-demethylhomolycorine and 5α-hydroxyhomolycorine. Alkaloids of Crinum defixum, C. scabrum, and C. latifolium. Assignment of aromatic substitution patterns from ¹H-coupled ¹³C spectra. J Org Chem. 1985; 50 1732-7
9 Kihara M, Konishi K, Xu L, Kobayashi S. Alkaloidal constituents of the flower of Lycoris radiata Herb. (Amaryllidaceae). Chem Pharm Bull. 1991; 39 1849-53
10 Boit H G, Döpke W. Alkaloide aus Hippeastrum aulicum var. robustum . Naturwissenschaften. 1960; 47 109
11 Evidente A, Cicala M R, Randazzo G, Riccio R, Calabrese G, Liso R. et al . Lycorine structure-activity relationships. Phytochemistry. 1983; 22 2193-6
12 Weislow O S, Kiser R, Fine D L, Bader J, Shoemaker R H, Boyd M R. New soluble formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J Natl Cancer Inst. 1989; 81 577-86
13 Campbell W E, Nair J J, Gammon D W, Bastida J, Codina C, Viladomat F, Smith P J, Albrecht C F. Cytotoxic and Antimalarial Alkaloids from Brunsvigia littoralis . Planta Medica. 1998; 64 91-3
14 Southon I W, Buckingham J. Dictionary of Alkaloids. London, New York; Chapman and Hall 1989: pp. 513 and 664
15 Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y. et al . Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981; 294 770-1
16 Aldovini A, Walker B D. Techniques in HIV Research. 1990 Stockton Press
17 Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65 55-63
18 Ayisi N K, Nyadedzor C. Comparative in vitro effects of AZT and extracts of Ocimum gratissimum, Ficus polita, Clausena anisata, Alchornea cordifolia, and Elaeophorbia drupifera against HIV-1 and HIV-2 infections. Antivir Res. 2003; 58 25-33
19 Somogyi P A, Gyuris Á, Földes I. A solid phase reverse transcriptase micro-assay for the detection of human immunodeficiency virus and other retroviruses in cell culture supernatants. J Virol Methods. 1990; 27 269-76

Dr. Judit Hohmann

Department of Pharmacognosy

University of Szeged

6720 Szeged

Hungary

Fax: +36-62-545-704

Email: hohmann@pharma.szote.u-szeged.hu