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Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi
We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2mug/ml concentration, respectively. Microfilariae (mf) were killed at 250-500mug/ml. The half maximal inhibitory concentration (IC50) of naringenin for motility of adult females was 2.5mug/ml. Flavone immobilized female adult worms at 31.2mug/ml (MTT>80%) and microfilariae at 62.5mug/ml. Rutin killed microfilariae at 125mug/ml and inhibited MTT-reduction in female worms for >65% at 500mug/ml. Naringin had adulticidal effects at 125mug/ml while chrysin killed microfilariae at 250mug/ml. In vivo, 50mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.
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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI