title: Anti-African trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic analogues.
abstract: OBJECTIVE
  The known anti-protozoal activity of flavonoids has stimulated the testing of other derivatives from natural and synthetic sources.
  
  
  METHODS
  As part of our efforts to find potential lead compounds, a number of flavonoids isolated from Neoraputia paraensis, N. magnifica, Murraya paniculata, (Rutaceae), Lonchocarpus montanus, L. latifolius, L. subglaucescens, L. atropurpureus, L. campestris, Deguelia hatschbachii (Leguminosae), dibenzoylmethanes from L. subglaucescens and synthetic analogues were tested for in-vitro activity against chloroquine-sensitive Plasmodium falciparum and Trypanosoma brucei rhodesiense bloodstream form trypomastigotes. An assay with KB cells has been developed in order to compare in-vitro cytotoxicity of flavonoids with a selective action on the parasites.
  
  
  RESULTS
  Thirteen of the compounds tested had IC50 values ranging from 4.6 to 9.9 microm against T. brucei rhodesiense. In contrast, a small number of compounds showed significant activity against P. falciparum; seven of those tested had IC50 values ranging from 2.7 to 9.5 microm. Among the flavones only one had IC50 < 10 microm (7.6 microm), whereas against T. brucei rhodesiense seven had IC50 < 10 microm. Synthetic dibenzoylmethanes were the most active in terms of number (five) of compounds and the IC50 values (2.7-9.5 microm) against P. falciparum.
  
  
  CONCLUSIONS
  Dibenzoylmethanes represent a novel class of compounds tested for the first time as antimalarial and trypanocidal agents.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, São Carlos, Brazil.
authors.forename: Djalma A P
authors.initials: DA
authors.lastname: dos Santos
authors.forename: Patricia A
authors.initials: PA
authors.lastname: de C Braga
authors.forename: M Fátima das G F
authors.initials: MF
authors.lastname: da Silva
authors.forename: João B
authors.initials: JB
authors.lastname: Fernandes
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Vieira
authors.forename: Aderbal F
authors.initials: AF
authors.lastname: Magalhães
authors.forename: Eva G
authors.initials: EG
authors.lastname: Magalhães
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Marsaioli
authors.forename: Valéria R
authors.initials: VR
authors.lastname: de S Moraes
authors.forename: Lauren
authors.initials: L
authors.lastname: Rattray
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D047188:Chalcones / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D050150:Chalones / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends; D055808:Drug Discovery; D007887:Fabaceae / Q000737:chemistry; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D027821:Rutaceae / Q000737:chemistry; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
chemical_list: D000962:Antimalarials; D047188:Chalcones; D050150:Chalones; D005419:Flavonoids; D014344:Trypanocidal Agents