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

BMC Complementary and Alternative Medicine

Isaiah O Ndiege⁷  Reto Brun²  Matthias Hamburger⁶  Petur Dalsgaard⁶  Daniel Häussinger¹  Urs Séquin¹  Ahmed Hassanali⁴  Maurice O Omolo⁵  Sauda M Swaleh⁷  Monical Cal²  Tanja Wenzler²  Hamisi M Malebo³ 

[1] Institute of Organic Chemistry, University of Basel, St Johanns Ring 19, Basel, CH-4052, Switzerland;Medical Parasitology and Infection Biology, Parasite Chemotherapy Unit, Swiss Tropical Institute, University of Basel, Socinstrasse 57, Basel, CH-4002, Switzerland;Department of Traditional Medicine Research, National Institute for Medical Research, P.O. Box 9653, Dar es Salaam, Tanzania;International Centre for Insect Physiology and Ecology, P.O. Box 30772, Nairobi, Kenya;Department of Pure and Applied Chemistry, Masinde Muliro University of Science & Technology, P. O. Box 190, Kakamega, Kenya;Institute of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, Basel, CH-4056, Switzerland;Department of Chemistry, Kenyatta University, P.O. Box 43844, Nairobi, Kenya

关键词: Cytotoxicity;    Antileishmanial;    Antitrypanosomal;    Antiplasmodial;    Protoberberine;    Aporphine;    Alkaloids;    Annonaceae;    Enantia kummeriae;    Annickia kummeriae;   

Others  :  1230294
DOI  :  10.1186/1472-6882-13-48

 received in 2012-10-29, accepted in 2013-02-04,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Malebo et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 1.

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