Aporphine Alkaloids from Guatteria spp. with Leishmanicidal Activity

Abstract

Fractionation of Guatteria amplifolia yielded the alkaloids xylopine (1), nornuciferine (4), lysicamine (6), and laudanosine (5). Fractionation of Guatteria dumetorum yielded the alkaloids cryptodorine (2) and nornantenine (3). Compounds 1 - 4 demonstrated significant activity against Leishmania mexicana and L. panamensis. Xylopine (1) was among the most active compounds (LD₅₀ = 3 μM) and showed a 37-fold higher toxicity towards L. mexicana than macrophages, the regular host cells of Leishmania spp.

References

• 1 Croat T B. Flora of Barro Colorado Island. Stanford, California; Stanford University Press 1978: p. 401
• 2 Weniger B, Aragon R, Deharo E, Bastida J, Codina C, Lobstein A, Anton R. Antimalarial constituents from Guatteria amplifolia .  Pharmazie. 2000;  55 867-8
• 3 Lopez J A, Laurito J G, Lin F T, Sharaf M, Wong L K, Schiff P L. Alkaloids of Guatteria diospyroides .  Planta Medica. 1993;  59 191
• 4 Weniger B, Robledo S, Arango G J, Deharo E, Aragon R, Munoz V, Callapa J, Lobstein A R. Antiprotozoal activities of Colombian plants.  Journal of Ethnopharmacology. 2001;  78 93-200
• 5 Kolodziej H, Kayser O, Kiderlen A F, Ito H, Hatano T, Yoshida T, Foo L Y. Antileishmanial activity of hydrolyzable tannins and their modulatory effects on nitric oxide and tumour necrosis factor-alpha release in macrophages in vitro .  Planta Medica. 2001;  67 825-32
• 6 Fuchino H, Koide T, Takahashi M, Sekita S, Satake M. New sesquiterpene lactones from Elephantopus mollis and their leishmanicidal activities.  Planta Medica. 2001;  67 647-53
• 7 Guinaudeau H, Leboeuf M, Cavé A. Aporphinoid alkaloids, III.  Journal of Natural Products. 1983;  46 761-835
• 8 Hocquemiller R, Rasamizafy S, Cavé A. Alcaloïdes des Annonacees XXXVII: alcaloides du Guatteria scandens .  Journal of Natural Products. 1983;  46 335-41
• 9 Guinaudeau H, Leboeuf M, Cavé A. Aporphinoid alkaloids.  Lloydia. 1975;  38 275-335
• 10 Mahiou V, Roblot F, Fournet A, Hocquemiller R. Bisbenzylisoquinoline alkaloids from Guatteria boliviana (Annonaceae).  Phytochemistry. 2000;  54 709-16
• 11 Corrodi H, Hardegger E. The configuration of natural (+)-laudanosine as well as related tetrahydroisoquinoline, aporphine, and tetrahydroberberine alkaloids.  Helv Chim Acta. 1956;  39 889-97
• 12 Morel C M. Genes and antigens of parasites. A laboratory manual. Second edition. Río de Janeiro, Brazil; Graphos editors 1984: p. 67
• 13 De Logu A, Uda P, Pellerano M L, Pusceddu M C, Saddi B, Schivo M. Comparison of two rapid colorimetric methods for determining resistance of Mycobacterium tuberculosis to rifampin, isoniazid, and streptomycin in liquid medium.  Eur J Clin Microbiol Infect Dis. 2001;  20 33-9
• 14 Golenser J, Frankenburg S, Ehrenfreund T, Domb A J. Efficacious treatment of experimental leishmaniasis with amphotericin B-arabinogalactan water-soluble derivatives.  Antimicrob Agents Chemother. 1999;  43 2209-14
• 15 Shin I S, Tanifuji H, Arata Y, Morizawa Y, Nakayama T, Wataya Y. 3′-Deoxy-3′-fluoroinosine as a potent antileishmanial agent. The metabolism and selective cytotoxic effect of 3′-deoxy-3′-fluoroinosine against Leishmania tropica and L. donovani in vitro and in vivo .  Parasitol Res. 1995;  81 622-6