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.
- Andrade AA, de Pilla Varotti L, de Freitas IO, de Souza MV, Vasconcelos TR, Boechat N, Krettli AU (2007) Enhanced activity of mefloquine and artesunic acid against Plasmodium falciparum in vitro and Plasmodium berghei in mice by combination with ciprofloxacin. Eur J Pharmacol 558:194–198CrossRefPubMedGoogle Scholar
- Andrade-Neto VF, Goulart MOF, Filho JFS, Silva MJ, Pinto MCFR, Pinto AV, Zalis MG, Carvalho LH, Krettli AU (2004) Antimalarial activity of phenazines from lapachol, β-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Bioorg Med Chem Lett 14:1145–1149CrossRefPubMedGoogle Scholar
- Froelich S, Onegi B, Kakooko A, Siems K, Schubert C, Jenett-Siems K (2007) Plants traditionally used against malaria: phytochemical and pharmacological investigation of Momordica foetida. Braz J Pharmacogn 17:1–7Google Scholar
- Junior CC, Marques C, Alencar FEC, Durlacher RR, Alween A, Segurado AAC, Pang LW, Zalis MG (1999) Antimalarial drug susceptibility testing of plasmodium falciparum in Brazil using a radioisotope method. Mem Inst Oswaldo Cruz 94:803–809Google Scholar
- Schlitzer M (2007) Malaria chemotherapeutics part I: history of antimalarial drug development, currently used therapeutics and drugs in clinical development. Chem Enab Drug Disc 7:944–986Google Scholar
- WHO (2001) Drug resistance in malaria. WHO/CDS/CSR/DRS/2001.4 GenevaGoogle Scholar
- WHO (2005) Global malaria situation. World Health Organization. World malaria report Geneva. http://whqlibdoc.who.int/publications/2005/9241593199_section1_eng.pdf[accesses 28 July 2008]
- WHO (2008) The use of antimalarial drugs. Part I: policy implications. Current status of antimalarial drug resistance. World Health Organization, Geneva. http://www.who.int/malaria/cmc_upload/0/000/014/923/am_toc.htm[accesses 27 July 2008].