title: Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae).
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).
  
  
  CONCLUSIONS
  The strong anti-plasmodial activity makes these alkaloids good lead structures for drug development programs.
authors: Department of Traditional Medicine Research, National Institute for Medical Research, P.O. Box 9653, Dar es Salaam, Tanzania. Malebo@hotmail.com
authors: Hamisi M
authors: HM
authors: Malebo
authors: Tanja
authors: T
authors: Wenzler
authors: Monical
authors: M
authors: Cal
authors: Sauda M
authors: SM
authors: Swaleh
authors: Maurice O
authors: MO
authors: Omolo
authors: Ahmed
authors: A
authors: Hassanali
authors: Urs
authors: U
authors: Séquin
authors: Daniel
authors: D
authors: Häussinger
authors: Petur
authors: P
authors: Dalsgaard
authors: Matthias
authors: M
authors: Hamburger
authors: Reto
authors: R
authors: Brun
authors: Isaiah O
authors: IO
authors: Ndiege
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D000962:Antimalarials / Q000032:analysis / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000032:analysis / Q000494:pharmacology*; D001060:Aporphines / Q000032:analysis / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000032:analysis / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D018515:Plant Leaves; D010963:Plasmodium falciparum / Q000187:drug effects*; D011528:Protozoan Infections / Q000188:drug therapy; D013636:Tanzania; D014344:Trypanocidal Agents / Q000032:analysis / Q000494:pharmacology; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D001060:Aporphines; D001600:Berberine Alkaloids; D010936:Plant Extracts; D014344:Trypanocidal Agents; C081279:aporphine; C009090:protoberberine