Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae)"

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Date
201
Authors
Malebo, H. M.
Wenzler, Tanja
Cal, Monical
Swaleh, Sauda M.
Omolo, Maurice O
Hassanali, Ahmed
Séquin, Urs
Häussinger, Daniel
Dalsgaard, P.
Hamburger, Matthias
Journal Title
Journal ISSN
Volume Title
Publisher
BMC Complementary and Alternative Medicine
Abstract
Background: Malaria, trypanosomiasis and leishmaniasis have an overwhelming impact in the poorest countries in the world due to their prevalence, virulence and drug resistance ability. Currently, there is inadequate armory of drugs for the treatment of malaria, trypanosomiasis and leishmaniasis. This underscores the continuing need for the discovery and development of new anti-protozoal drugs. Consequently, there is an urgent need for research aimed at the discovery and development of new effective and safe anti-plasmodial, anti-trypanosomal and anti-leishmanial drugs. Methods: Bioassay-guided chromatographic fractionation was employed for the isolation and purification of antiprotozoal alkaloids. Results: The methanol extract from the leaves of Annickia kummeriae from Tanzania exhibited a strong anti-plasmodial activity against the multi-drug resistant Plasmodium falciparum K1 strain (IC50 0.12 ± 0.01 µg/ml, selectivity index (SI) of 250, moderate activity against Trypanosoma brucei rhodesiense STIB 900 strain (IC50 2.50 ± 0.19 µg/ml, SI 12) and mild activity against Leishmania donovani axenic MHOM-ET-67/82 strain (IC50 9.25 ± 0.54 µg/ml, SI 3.2). Bioassay-guided chromatographic fractionation led to the isolation of four pure alkaloids, lysicamine (1), trivalvone (2), palmatine (3), jatrorrhizine (4) and two sets of mixtures of jatrorrhizine (4) with columbamine (5) and palmatine (3) with (-)-tetrahydropalmatine (6). The alkaloids showed low cytotoxicity activity (CC50 30 - >90 µg/ml), strong to moderate anti-plasmodial activity (IC50 0.08 ± 0.001 - 2.4 ± 0.642 µg/ml, SI 1.5-1,154), moderate to weak anti-trypanosomal (IC50 2.80 ± 0.001 - 14.3 ± 0.001 µg/ml, SI 2.3-28.1) and anti-leishmanial activity IC50 2.7 ± 0.001 - 20.4 ± 0.003 µg/ml, SI 1.7-15.6). Conclusion: The strong anti-plasmodial activity makes these alkaloids good lead structures for drug development programs.
Description
doi:10.1186/1472-6882-13-48
Keywords
Annickia kummeriae, Enantia kummeriae, Annonaceae, Alkaloids, Aporphine, Protoberberine, Antiplasmodial, Antitrypanosomal, Antileishmanial, Cytotoxicity
Citation
BMC Complementary and Alternative Medicine 2013, 13:48