Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice
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Malaria is one of the most important tropical diseases and mainly affects populations living in developing countries. Reduced sensitivity of Plasmodium sp. to formerly recommended antimalarial drugs places an increasing burden on malaria control programs as well as on national health systems in endemic countries. The present study aims to evaluate the antimalarial activity of betulinic acid and its derivative compounds, betulonic acid, betulinic acid acetate, betulinic acid methyl ester, and betulinic acid methyl ester acetate. These substances showed antiplasmodial activity against chloroquine-resistant Plasmodium falciparum parasites in vitro, with IC50 values of 9.89, 10.01, 5.99, 51.58, and 45.79 μM, respectively. Mice infected with Plasmodium berghei and treated with betulinic acid acetate had a dose-dependent reduction of parasitemia. Our results indicate that betulinic acid and its derivative compounds are candidates for the development of new antimalarial drugs.
KeywordsMalaria Chloroquine Mefloquine Antimalarial Activity Betulinic Acid
The authors wish to thank Fabrício Souza Silva for technical assistance. The experiments made in this study comply with the current laws of the Brazil. The approval for this work was obtained from the Ethics Committee on the Use of Laboratorial Animals (reference number 004/2002). This work received financial support from FIOCRUZ, RENORBIO, CNPq, FINEP, MCT, and INSEAR.
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