Antimalarial activity of triterpenoids with the cucurbitane skeleton
Malaria, caused by protozoan parasites of the genus Plasmodium, is a devastating infectious disease in tropical and subtropical countries. One of the biggest problems that have hindered the control of malaria is the emergence and spread of drug resistant Plasmodium strains, particularly Plasmodium falciparum. In order to overcome this problem, new therapeutic agents based on new mechanisms of action or with new structures are urgently needed. Plants have been an important source of medicines against malaria. Quinine and artemisinin, two of the most important antimalarials currently in use, were derived from plants [1,2]. Momordica balsamina L. (Cucurbitaceae), a vegetable used as food, has also been widely used in traditional medicine, mainly for the treatment of fever and malaria in Mozambique and South Africa . Continuing our search for biologically active compounds from Momordica balsamina [4,5], the bioassay-guided fractionation of the methanol extract of the aerial parts of this plant led to the isolation of three new cucurbitane-type triterpenoids, balsaminols C-E. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY). These compounds together with ten cucurbitane-type triterpenoids previously isolated [4,5] were evaluated for their antimalarial activity against two different P. falciparum strains (3D7 and Dd2). Their cytotoxicity was also assayed against human breast cancer cells (MCF-7). Most of the compounds displayed antimalarial activity against both the chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2 of P. falciparum. They were inactive or showed weak toxicity against the MCF-7 cell line.
Acknowledgements: The authors wish to thank the Science and Technology Foundation, (FCT, grant SFRH/BD/22321/2005).
References: 1. Turschner, S. et al (2009) Mini-Rev. Med. Chem. 9: 206–14.
2. Wells, T.N.S. et al (2009) Nat. Rev. Drug Discov., 8: 879–91.
3. Bandeira, S.O. et al (2001) Pharm. Biol. 39: 70–3.
4. Ramalhete, C. et al (2009) Bioorg. Med. Chem. 17: 6942–51.
5. Ramalhete, C. et al. J. Nat. Prod. 72: 2009–13.