Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice.
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 IC(50) values of 9.89, 10.01, 5.99, 51.58, and 45.79 microM, 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.
de Sá
Matheus Santos
MS
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
Costa
José Fernando Oliveira
JF
Krettli
Antoniana Ursine
AU
Zalis
Mariano Gustavo
MG
Maia
Gabriela Lemos de Azevedo
GL
Sette
Ivana Maria Fechine
IM
Câmara
Celso de Amorim
Cde A
Filho
José Maria Barbosa
JM
Giulietti-Harley
Ana Maria
AM
Ribeiro Dos Santos
Ricardo
R
Soares
Milena Botelho Pereira
MB
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D016019:Survival Analysis; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D000094062:Betulinic Acid
D000962:Antimalarials; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid