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.
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
Matheus Santos
MS
de Sá
José Fernando Oliveira
JF
Costa
Antoniana Ursine
AU
Krettli
Mariano Gustavo
MG
Zalis
Gabriela Lemos de Azevedo
GL
Maia
Ivana Maria Fechine
IM
Sette
Celso de Amorim
Cde A
Câmara
José Maria Barbosa
JM
Filho
Ana Maria
AM
Giulietti-Harley
Ricardo
R
Ribeiro Dos Santos
Milena Botelho Pereira
MB
Soares
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