Résumé
The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC50 of 48.5 æM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60 percent at 20 æg/ml (59 and 90 æM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 æg/ml (0.6-1.5 mM).
Sujets)
Animaux , Mâle , Souris , Furanes/pharmacologie , Antienzymes/pharmacologie , NADH, NADPH oxidoreductases/antagonistes et inhibiteurs , Trypanocides/pharmacologie , Trypanosoma cruzi/effets des médicaments et des substances chimiques , Furanes/composition chimique , Antienzymes/composition chimique , Relation structure-activitéRésumé
Fourteen compounds were evaluated for their activity against Trypanosoma cruzi blood stream forms at the concentration of 500 æg/ml. Six compounds were active and re-tested at lower concentrations