Anti-African trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic analogues.
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.
dos Santos
Djalma A P
DA
Departamento de Química, Universidade Federal de São Carlos, São Carlos, Brazil.
de C Braga
Patricia A
PA
da Silva
M Fátima das G F
MF
Fernandes
João B
JB
Vieira
Paulo C
PC
Magalhães
Aderbal F
AF
Magalhães
Eva G
EG
Marsaioli
Anita J
AJ
de S Moraes
Valéria R
VR
Rattray
Lauren
L
Croft
Simon L
SL
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
D000962:Antimalarials; D047188:Chalcones; D050150:Chalones; D005419:Flavonoids; D014344:Trypanocidal Agents