Research
Antimalarial activity of a cis-terpenone
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* Corresponding author: DC Ghislaine Mayer gmayer@vcu.edu
1 Department of Biology, Virginia Commonwealth University, 1000 W. Cary St, Richmond, Virginia, 23284-2012, USA
2 Department of Chemistry, Virginia Commonwealth University, 1001 W. Main St, Richmond, Virginia, 23284-2006, USA
Malaria Journal 2009, 8:139 doi:10.1186/1475-2875-8-139
Published: 25 June 2009Abstract
Background
Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy-cis terpenone (OHCT) is a synthetic molecule that is not toxic to cultured human liver cells at concentrations as high as 60 μM and inhibits activity of cytochrome P450s that metabolize many drugs.
Methods
OHCT activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, and a P. falciparum clone that is partially resistant to artemisinin was assayed in vitro.
Results
OHCT at nanomolar concentrations was effective against all intraerythrocytic stages of P. falciparum and exhibited activity in vitro against both chloroquine-sensitive and -resistant strains of P. falciparum as well as a P. falciparum clone that is partially resistant to artemisinin. Moreover, OHCT exhibited potent activity against gametocytes, the form that is transmitted by mosquitoes and essential for the spread of malaria.
Conclusion
OHCT displays strong growth inhibitory activity against all stages of P. falciparum and no evidence of toxicity to human cells in culture. It is easily synthesized and has the potential for inhibiting metabolism of drugs used in combination therapies.