Antimalarial activity of a cis-terpenone.
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 microM 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.


CONCLUSIONS
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.
Mayer
D C Ghislaine
DC
Department of Biology, Virginia Commonwealth University, Richmond, Virginia 23284-2012, USA. gmayer@vcu.edu
Bruce
Maimuna
M
Kochurova
Olga
O
Stewart
Jennifer K
JK
Zhou
Qibing
Q
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured / Q000187:drug effects; D004351:Drug Resistance; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013729:Terpenes / Q000138:chemical synthesis / Q000494:pharmacology*
D000962:Antimalarials; D013729:Terpenes