title: A characterization of the antimalarial activity of the bark of Cylicodiscus gabunensis Harms.
abstract: A decoction of the bark of Cylicodiscus gabunensis Harms is used as a traditional medicine in the treatment of malaria in Nigeria. This study aims to validate the antimalarial potency of this decoction in vitro against Plasmodium falciparum and define potential bioactive constituents within the C. gabunensis bark.
  
  
  METHODS
  A bioassay-guided separation and fractionation protocol was applied to C. gabunensis extracts, exploiting the use of a Malaria Sybr Green I Fluorescence assay method to monitor antiproliferative effects on parasites as well as define 50% inhibition concentrations. Spectroscopic techniques, including GC-MS, TOF LC-MS and1H NMR were used to identify phytochemicals present in bioactive fractions. Analogues of gallic acid were synthesized de novo to support the demonstration of the antimalarial action of phenolic acids identified in C. gabunensis bark. In vitro cytotoxicity of plant extracts, fractions and gallate analogues was evaluated against the HepG2 cell line.
  
  
  RESULTS
  The antimalarial activity of ethanolic extracts of C. gabunensis bark was confirmed in vitro, with evidence for phenolic acids, primarily gallic acid and close analogues such as ethyl gallate, likely providing this effect. Further fractionation produced the most potent fraction with a 50% inhibitory concentration of 4.7µg/ml. Spectroscopic analysis, including1H NMR, LC-MS and GC-MS analysis of this fraction and its acid hydrolyzed products, indicated the presence of conjugates of gallic acid with oligosaccharides. The extracts/fractions and synthetic alkyl and alkenyl gallates showed moderate selectivity against P. falciparum.
  
  
  CONCLUSIONS
  These results support the use of the bark of C. gabunensis as a traditional medicine in the treatment of human malaria, with phenolic acid oligosaccharide complexes evident in the most bioactive fractions.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom; College of Pharmacy, Al-Mustansiriyah University, Baghdad, Iraq.
authors.forename: Omar
authors.initials: O
authors.lastname: Aldulaimi
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Fidelia I
authors.initials: FI
authors.lastname: Uche
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Hamza
authors.initials: H
authors.lastname: Hameed
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Haddijatou
authors.initials: H
authors.lastname: Mbye
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Imran
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Chemical Sciences Research Centre, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Falko
authors.initials: F
authors.lastname: Drijfhout
authors.affiliation: Chemical Research Laboratory, University of Oxford, Oxford OX1 3TA, United Kingdom.
authors.forename: Timothy D W
authors.initials: TDW
authors.lastname: Claridge
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Horrocks
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Staffordshire ST5 5BG, United Kingdom. Electronic address: w.li@keele.ac.uk.
authors.forename: Wen-Wu
authors.initials: WW
authors.lastname: Li
mesh_terms: D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology*; D002853:Chromatography, Liquid; D007887:Fabaceae / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D016778:Malaria, Falciparum / Q000188:drug therapy; D013058:Mass Spectrometry; D016488:Medicine, African Traditional; D009549:Nigeria; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D010936:Plant Extracts
keywords: Cylicodiscus gabunensis; Gallic acid; Malaria; Oligosaccharide conjugates; Structural elucidation